Papers - MATSUKAWA Akihiro

Redox-active protein Thioredoxin-1 administration ameliorates influenza a virus (H1N1)-induced acute lung injury in mice Reviewed International journal

Masato Yashiro, Hirokazu Tsukahara, Akihiro Matsukawa, Mutsuko Yamada, Yosuke Fujii, Yoshiharu Nagaoka, Mitsuru Tsuge, Nobuko Yamashita, Toshihiro Ito, Masao Yamada, Hiroshi Masutani, Junji Yodoi, Tsuneo Morishima

Critical Care Medicine   41 ( 1 )   171 - 181   2013.1

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OBJECTIVES:: Influenza virus infections can cause severe acute lung injury leading to significant morbidity and mortality. Thioredoxin-1 is a redox-active defensive protein induced in response to stress conditions. Animal experiments have revealed that thioredoxin-1 has protective effects against various severe disorders. This study was undertaken to evaluate the protective effects of recombinant human thioredoxin-1 administration on influenza A virus (H1N1)-induced acute lung injury in mice. DESIGN:: Prospective animal trial. SETTING:: Research laboratory. SUBJECTS:: Nine-week-old male C57BL/6 mice inoculated with H1N1. INTERVENTION:: The mice were divided into a vehicle-treated group and recombinant human thioredoxin-1-treated group. For survival rate analysis, the vehicle or recombinant human thioredoxin-1 was administered intraperitoneally every second day from day-1 to day 13. For lung lavage and pathological analyses, vehicle or recombinant human thioredoxin-1 was administered intraperitoneally on days-1, 1, and 3. MEASUREMENTS AND MAIN RESULTS:: Lung lavage and pathological analyses were performed at 24, 72, and 120 hrs after inoculation. The recombinant human thioredoxin-1 treatment significantly improved the survival rate of H1N1-inoculated mice, although the treatment did not affect virus propagation in the lung. The treatment significantly attenuated the histological changes and neutrophil infiltration in the lung of H1N1-inoculated mice. The treatment significantly attenuated the production of tumor necrosis factor-α and chemokine (C-X-C motif) ligand 1 in the lung and oxidative stress enhancement, which were observed in H1N1-inoculated mice. H1N1 induced expressions of tumor necrosis factor-α and chemokine (C-X-C motif) ligand 1 in murine lung epithelial cells MLE-12, which were inhibited by the addition of recombinant human thioredoxin-1. The recombinant human thioredoxin-1 treatment started 30 mins after H1N1 inoculation also significantly improved the survival of the mice. CONCLUSIONS:: Exogenous administration of recombinant human thioredoxin-1 significantly improved the survival rate and attenuated lung histological changes in the murine model of influenza pneumonia. The protective mechanism of thioredoxin-1 might be explained by its potent antioxidative and anti-inflammatory actions. Consequently, recombinant human thioredoxin-1 might be a possible pharmacological strategy for severe influenza virus infection in humans. © 2013 by the Society of Critical Care Medicine and Lippincott Williams &amp
Wilkins.

DOI： 10.1097/CCM.0b013e3182676352

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妊娠中に発症し高度のネフローゼを呈した急性糸球体腎炎の生検例

伏見 聡一郎, 桑本 聡史, 野坂 加苗, 徳安 祐輔, 中本 周, 上浦 望, 尾田 高志, 城 謙輔, 松川 昭博

診断病理   30 ( 1 )   66 - 70   2013.1

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Language：Japanese   Publisher：(一社)日本病理学会  

症例は妊娠中の20代女性。高度のネフローゼ症候群を呈し、腎生検が行われた。組織学的に糸球体の腫大と管内への炎症細胞浸潤を認めた。免疫染色では有意な所見は得られなかったが、組織化学的に糸球体でplasmin活性が認められ、溶連菌感染後急性糸球体腎炎と考えられた。本例の鑑別診断においてplasmin活性の酵素組織化学的所見が意義あると考えられた。文献的考察も加えて報告する。(著者抄録)

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Occult Compression Fracture of Metacarpal Head without Evidence of Avascular Necrosis. Reviewed

Keiichiro Nishida, Hiroyuki Hashizume, Akihiro Matsukawa, Kenzo Hashizume, Yasunori Shimamura, Yasuyuki Torigoe, Toshifumi Ozaki

Acta medica Okayama   67 ( 5 )   311 - 7   2013

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We report a case of 4th metacarpal head collapse of a 19-year-old healthy man. MRI revealed T1 low and T2 high regions in the collapsed 4th metacarpal head, as well as in the right 3rd and left 4th metacarpal head. Our initial diagnosis was occult compression fracture due to avascular necrosis, known as Dieterich's disease. However, pathological findings of surgically resected right 4th metacarpal head were compatible with transient osteoporosis and metacarpal head fracture followed by active tissue repair. The autologous osteochondral transplants from costchondral junction survived and maintained their size and shape even at 10-year follow-up.

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Therapeutic effects of redox-active protein thioredoxin(TRX)-1 in influenza-virus-induced pneumonia in mice

YASHIRO MASATO, TSUKAHARA HIROKAZU, MATSUKAWA AKIHIRO, YAMADA MUTSUKO, FUJII YOSUKE, NAGAOKA YOSHIHARU, TSUGE MITSURU, YAMASHITA NOBUKO, ITO TOSHIHIRO, YAMADA MASAO, MASUTANI HIROSHI, YODOI JUNJI, MORISHIMA TSUNEO

岡山医学会雑誌   125 ( 2 )   109-112 (J-STAGE) - 112   2013

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Language：Japanese  

DOI： 10.4044/joma.125.109

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Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells. Reviewed International journal

Yoshimura T, Howard OM, Ito T, Kuwabara M, Matsukawa A, Chen K, Liu Y, Liu M, Oppenheim JJ, Wang JM

PloS one   8 ( 3 )   e58791   2013

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MCP-1/CCL2 plays an important role in the initiation and progression of cancer. Since tumor cells produce MCP-1, they are considered to be the main source of this chemokine. Here, we examined whether MCP-1 produced by non-tumor cells affects the growth and lung metastasis of 4T1 breast cancer cells by transplanting them into the mammary pad of WT or MCP-1(-/-) mice. Primary tumors at the injected site grew similarly in both mice; however, lung metastases were markedly reduced in MCP-1(-/-) mice, with significantly longer mouse survival. High levels of MCP-1 mRNA were detected in tumors growing in WT, but not MCP-1(-/-) mice. Serum MCP-1 levels were increased in tumor-bearing WT, but not MCP-1(-/-) mice. Transplantation of MCP-1(-/-) bone marrow cells into WT mice did not alter the incidence of lung metastasis, whereas transplantation of WT bone marrow cells into MCP-1(-/-) mice increased lung metastasis. The primary tumors of MCP-1(-/-) mice consistently developed necrosis earlier than those of WT mice and showed decreased infiltration by macrophages and reduced angiogenesis. Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of MCP-1, and intravenous injection of 4T1 cells producing a high level of MCP-1 resulted in increased tumor foci in the lung of WT and MCP-1(-/-) mice. Thus, stromal cell-derived MCP-1 in the primary tumors promotes lung metastasis of 4T1 cells, but tumor cell-derived MCP-1 can also contribute once tumor cells enter the circulation. A greater understanding of the source and role of this chemokine may lead to novel strategies for cancer treatment.

DOI： 10.1371/journal.pone.0058791

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The linkage of innate and adaptive immune response during granulomatous development. Reviewed International journal

Ito T, Connett JM, Kunkel SL, Matsukawa A

Frontiers in immunology   4   10 - 10   2013

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Granulomas represent a spectrum of inflammatory sequestration responses that may be initiated by a variety of agents, including non-infectious environmental factors and infectious microbial pathogens. Although this reaction is designed to be protective, the associated tissue injury is often responsible for a profound degree of pathology. While many of the mechanisms that sustain the development of the granuloma are enigmatic, it is accepted that the maintenance of this inflammatory process is dependent upon dynamic interactions between an inciting agent, inflammatory mediators, various immune and inflammatory cells, and structural cells of the involved tissue. The best studied of the host-dependent processes during granuloma development is the innate and adaptive immune response. The innate immune response by antigen-presenting cells [APCs; dendritic cells (DCs) and macrophages] is initiated quickly to protect from overwhelming pathogens, but with time, can also activate the adaptive immune response. APCs, essential regulators of the innate immune response, can respond to microbial ligands through Toll-like receptors (TLRs), which function in the recognition of microbial components and play an important role to link the innate and adaptive immune responses. CD4(+) T helper (Th) cells are essential regulators of adaptive immune responses and inflammatory diseases. Recently, the Notch system has been shown to be an important bridge between APCs and T cell communication circuits. In the present review, we discuss recent findings that explore the mechanisms in the linkage of innate and adaptive immunity, including granulomatous formation though TLRs and Notch activation.

DOI： 10.3389/fimmu.2013.00010

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Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4. Reviewed International journal

Yasuyuki Shiozaki, Takashi Kitajima, Tetsuro Mazaki, Aki Yoshida, Masato Tanaka, Akihiro Umezawa, Mariko Nakamura, Yasuhiro Yoshida, Yoshihiro Ito, Toshifumi Ozaki, Akihiro Matsukawa

International journal of nanomedicine   8   1349 - 60   2013

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PURPOSE: Bone defects and nonunions are major clinical skeletal problems. Growth factors are commonly used to promote bone regeneration; however, the clinical impact is limited because the factors do not last long at a given site. The introduction of tissue engineering aimed to deter the diffusion of these factors is a promising therapeutic strategy. The purpose of the present study was to evaluate the in vivo osteogenic capability of an engineered bone morphogenetic protein-4 (BMP4) fusion protein. METHODS: BMP4 was fused with a nanosized carrier, collagen-binding domain (CBD), derived from fibronectin. The stability of the CBD-BMP4 fusion protein was examined in vitro and in vivo. Osteogenic effects of CBD-BMP4 were evaluated by computer tomography after intramedullary injection without a collagen-sponge scaffold. Recombinant BMP-4, CBD, or vehicle were used as controls. Expressions of bone-related genes and growth factors were compared among the groups. Osteogenesis induced by CBD-BMP4, BMP4, and CBD was also assessed in a bone-defect model. RESULTS: In vitro, CBD-BMP4 was retained in a collagen gel for at least 7 days while BMP4 alone was released within 3 hours. In vivo, CBD-BMP4 remained at the given site for at least 2 weeks, both with or without a collagen-sponge scaffold, while BMP4 disappeared from the site within 3 days after injection. CBD-BMP4 induced better bone formation than BMP4 did alone, CBD alone, and vehicle after the intramedullary injection into the mouse femur. Bone-related genes and growth factors were expressed at higher levels in CBD-BMP4-treated mice than in all other groups, including BMP4-treated mice. Finally, CBD-BMP4 potentiated more bone formation than did controls, including BMP4 alone, when applied to cranial bone defects without a collagen scaffold. CONCLUSION: Altogether, nanocarrier-CBD enhanced the retention of BMP4 in the bone, thereby promoting augmented osteogenic responses in the absence of a scaffold. These results suggest that CBD-BMP4 may be clinically useful in facilitating bone formation.

DOI： 10.2147/IJN.S44124

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Elevated Levels of Monocyte Chemoattractant Protein-1 in the Aqueous Humor after Phacoemulsification Reviewed International journal

Motofumi Kawai, Toshihiro Inoue, Masaru Inatani, Naoko Tsuboi, Kohei Shobayashi, Akihiro Matsukawa, Akitoshi Yoshida, Hidenobu Tanihara

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   53 ( 13 )   7951 - 7960   2012.12

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. To elucidate the impact of phacoemulsification on aqueous monocyte chemoattractant protein-1 (MCP-1) levels, and identify its cell origin.
METHODS. For clinical study, aqueous humor samples were collected before and after surgery (17.0 +/- 4.0 months postoperatively) from 21 cataract cases that underwent phacoemulsification and intraocular lens (IOL) implantation. Aqueous MCP-1 levels were determined using a multiplex immunoassay. For animal experiments, rabbits underwent phacoemulsification (+/- IOL). Aqueous humor samples were collected from nonoperated eyes and operated eyes, and immunoassays were performed. Eyes were analyzed by reverse transcription-polymerase chain reaction and immunohistochemical studies.
RESULTS. In the clinical study, mean (+/- SD) aqueous MCP-1 levels were higher postoperatively (1773.5 +/- 321.2 pg/mL) than preoperatively (796.9 +/- 211.3 pg/mL; P < 0.0001). In animal experiments, mean aqueous MCP-1 levels (pg/mL) were higher in postoperative eyes on day 30 (207.1 +/- 62.9) than in nonoperated eyes (31.2 +/- 12.5; P = 0.018). IOL implantation did not affect the changes in MCP-1 levels. After phacoemulsification, MCP-1 mRNA expression was increased in the cornea, iris, ciliary body, and capsular bag. Expression of MCP-1 mRNA in the capsular bag, but not the other tissues, increased from day 30 to 90. Immunohistochemical studies showed positive immunoreactivity for MCP-1 in cells of the posterior capsule after phacoemulsification.
CONCLUSIONS. Aqueous MCP-1 levels were elevated in both human and animal eyes after phacoemulsification. Proliferated lens epithelial cells on the capsule might be the major cell origin for prolonged MCP-1 production after phacoemulsification. (http://www.umin.ac.jp/number, UMIN000005788.) (Invest Ophthalmol Vis Sci. 2012;53:7951-7960) DOI: 10.1167/iovs.12-10231

DOI： 10.1167/iovs.12-10231

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炎症の発現・制御におけるサイトカインシグナル伝達

松川 昭博

小児感染免疫   24 ( 3 )   303 - 307   2012.10

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Language：Japanese   Publisher：日本小児感染症学会  

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Spred-2 deficiency exacerbates acetaminophen-induced hepatotoxicity in mice Reviewed International journal

Hiroshi Wakabayashi, Toshihiro Ito, Soichiro Fushimi, Yuki Nakashima, Jyunya Itakura, Liu Qiuying, Min Min Win, Sun Cuiming, Cao Chen, Miwa Sato, Megumi Mino, Tetsuya Ogino, Hirofumi Makino, Akihiko Yoshimura, Akihiro Matsukawa

CLINICAL IMMUNOLOGY   144 ( 3 )   272 - 282   2012.9

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

MAPKs are involved in acetaminophen (APAP)-hepatotoxicity, but the regulatory mechanism remains unknown. Here, we explored the role of Spred-2 that negatively regulates Ras/ERK pathway in APAP-hepatotoxicity. Spred-2 knockout (KO) mice demonstrated exacerbated liver injury, an event that was associated with increased numbers of CD4(+) T, CD8(+) T and NK cells in the liver compared to the control. Levels of CXCL9/CXCL10 that attract and activate these cells were increased in Spred-2 KO-liver. Kupffer cells isolated from Spred-2 KO mice after APAP challenge expressed higher levels of CXCL9/CXCL10 than those from the control. Upon stimulation with APAP or IFN gamma, naive Kupffer cells from Spred-2 KO mice expressed higher levels of CXCL9/CXCL10. NK cell-depletion attenuated APAP-hepatotoxicity with lowered hepatic IFN gamma and decreased numbers of not only NK cells but also CD4(+) T and CD8(+) T cells in the liver. These results suggest that Spred-2 negatively regulates APAP-hepatotoxicity under the control of Kupffer cells and NK cells. (C) 2012 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.clim.2012.07.002

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Notch system in the linkage of innate and adaptive immunity. Reviewed International journal

Ito T, Connett JM, Kunkel SL, Matsukawa A

Journal of leukocyte biology   92 ( 1 )   59 - 65   2012.7

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The lung is one of the most immunologically challenged organs and can be affected by a number of pathogens, including bacteria, virus, fungi, and parasites. The development and chronicity of pulmonary infection are determined by the early innate response to the pathogenic stimuli and are regulated at multiple levels. Initial studies have indicated that the interaction of Notch and Notch ligands plays a critical role during development, and further, the Notch system is an important bridge between APCs and T cell communication circuits. APCs are essential regulators of the innate immune response. They can respond to PAMPs through PRRs, which function in the recognition of pathogenic components and play an important role in the innate and adaptive immune response. T cells are essential regulators of adaptive immune responses and infectious diseases. However, the role of the Notch system in the cross-talk between APC and T cells during pulmonary infection is still poorly understood. In the present review, we discuss recent findings that explore the mechanisms underlying the role of Notch signaling in the linkage of innate and adaptive immunity, including pulmonary infection though PPRs and Notch activation.

DOI： 10.1189/jlb.1011529

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Effects of Pharyngeal Cooling on Brain Temperature in Primates and Humans A Study for Proof of Principle Reviewed International journal

Yoshimasa Takeda, Hiroshi Hashimoto, Koji Fumoto, Tetsuya Danura, Hiromichi Naito, Naoki Morimoto, Hiroshi Katayama, Soichiro Fushimi, Akihiro Matsukawa, Aiji Ohtsuka, Kiyoshi Morita

ANESTHESIOLOGY   117 ( 1 )   117 - 125   2012.7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Background: Pharyngeal cooling decreases brain temperature by cooling carotid arteries. This study was designed to evaluate the principle of pharyngeal cooling in monkeys and humans.
Methods: Monkeys (n = 10) were resuscitated following 12 min of cardiac arrest. Pharyngeal cooling (n = 5), in which cold saline (5 degrees C) was perfused into the cuff at the rate of 500 ml/min, was initiated simultaneously with the onset of resuscitation for 30 min. Patients (n = 3) who were in an intensive care unit were subjected to 30 min of pharyngeal cooling under propofol anesthesia.
Results: In the animal study, core brain temperature was significantly decreased compared with that in the control group by 1.9 degrees C (SD = 0.8, P < 0.001) and 3.1 degrees C (SD = 1.0, P < 0.001) at 10 ruin and 30 min after the onset of cooling, respectively. The cooling effect was more evident in an animal with low postresuscitation blood pressure. Total dose of epinephrine, number of direct current shocks, and recovery of blood pressure were not different between the two groups. The pharyngeal epithelium was microscopically intact on day 5. In the clinical study, insertion of the cuff and start of perfusion did not affect heart rate or blood pressure. Tympanic temperature was decreased by 0.6 +/- 0.1 degrees C/30 min without affecting bladder temperature. The pharynx was macroscopically intact for 3 days.
Conclusions: Pharyngeal cooling rapidly and selectively decreased brain temperature in primates and tympanic temperature in humans and did not have adverse effects on return of spontaneous circulation, even when initiated during cardiac arrest in primates.

DOI： 10.1097/ALN.0b013e3182580536

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Spred-2 negatively regulates influenza A virus (H1N1)-induced pneumonia Reviewed

Toshihiro Ito, Akihiko Yoshimura, Akihiro Matsukawa

JOURNAL OF IMMUNOLOGY   188   2012.5

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Authorship：Last author,　Corresponding author   Language：English   Publisher：AMER ASSOC IMMUNOLOGISTS  

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Egr1: a novel target for ameliorating acute allograft rejection in an experimental lung transplant model Reviewed International journal

Naohisa Waki, Masaomi Yamane, Sumiharu Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Akihiro Matsukawa, Takahiro Oto, Shinichiro Miyoshi

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY   41 ( 3 )   669 - 675   2012.3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS INC  

Acute allograft rejection is one of the significant complications occurring in lung transplant recipients. Early growth response-1 (Egr-1), zinc-finger-type transcription factor, is known as a master switch regulator of diverse chemical mediators. We used an orthotopic mouse model of left lung transplant to elucidate the function of Egr-1 in acute pulmonary rejection.
Left lung grafts retrieved from C57BL/6 wild mice or C57BL/6 Egr-1-null mice were orthotopically transplanted into BALB/c mice; the lungs were harvested at day 1, 3, 5 or 7 after lung transplantation. The grade of acute rejection was histopathologically evaluated. The intragraft gene expression levels of Egr-1 and downstream target mediators were quantitatively measured by real-time polymerase chain reaction. Immunohistochemical analysis was used to determine the location and distribution of the Egr-1 protein in the pulmonary graft.
Severe acute rejection was observed in allografts from wild-type mice at 5 days after transplantation. Only minimal rejection was seen in the lung graft from Egr-1-null donor mice at 5 days after transplantation. Strong upregulation of Egr-1 mRNA transcripts was observed at day 1, which then decreased during the next 5 days. The mRNA of Egr-1 target mediators [interleukin-1-beta (IL-1 beta), monocyte chemotactic protein-1 (MCP-1) and plasminogen activator inhibitor-1] reached maximal levels at day 5. Egr-1-null allografts exhibited significantly lower expressions of IL-1 beta and MCP-1 mRNA (P < 0.05).
Our study showed that deletion of Egr-1 in lung allografts ameliorates severe acute rejection with the reduction of expression levels of chemical mediators, implying a new possible strategy for treating acute pulmonary allograft rejection.

DOI： 10.1093/ejcts/ezr030

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Local effects of intra-articular injection of anti-rabbit tumor necrosis factor alpha monoclonal antibody in antigen-induced arthritis of the rabbit temporomandibular joint Reviewed International journal

Taishi Ohtani, Manabu Habu, Amit Khanal, Izumi Yoshioka, Akihiro Matsukawa, Kazuhiro Tominaga

JOURNAL OF ORAL PATHOLOGY & MEDICINE   41 ( 1 )   96 - 105   2012.1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

BACKGROUND: Local effects of intra-articular (IA) injection of anti-rabbit tumor necrosis factor alpha monoclonal antibody (anti-TNF alpha mAb) for antigen-induced mono-arthritis (AIA) of the rabbit temporomandibular joint (TMJ) and its systemic influences were evaluated.
METHODS: Biochemical analysis of synovial fluid (SF), clinical and histopathological analyses of TMJ, and serum analysis were performed after inducing AIA in bilateral TMJs of 40 New Zealand White rabbits. IA injection of anti-TNF alpha mAb in unilateral TMJ (TNF blockade side; n = 12) and IgG (n = 12) was performed while saline injected on the contralateral side. TNF alpha and IL-1 beta in SF was analyzed at Days 1, 3, 7, and 21. Joint swelling and head withdrawal reflex threshold (WRT) over TMJs were evaluated in TNF blockade side (n = 12) with histopathological analysis at Days 3, 7, and 21. In remaining four animals with TNF blockade, TNF alpha and anti- TNF alpha mAb in serum were analyzed.
RESULTS: Tumor necrosis factor alpha in SF was significantly lower in TNF blockade side on all days but IL-1 beta was lower only on Day 3. WRT was significantly higher at all times in the blockade side. Less inflammatory reactions and degenerative changes of cartilage were observed on Days 7 and 21 in the blockade side. TNF alpha and anti- TNF alpha mAb were under detection level in serum at all times.
CONCLUSIONS: Intra-articular injection of anti- rabbit TNF alpha mAb in mono-arthritis model was effective to control local inflammation and degenerative joint changes. Further, low-dose IA injection of antibody may not have systemic side effects. J Oral Pathol Med (2012) 41: 96105

DOI： 10.1111/j.1600-0714.2011.01056.x

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Prostatic stromal tumor of uncertain malignant potential (STUMP) with unrecognized growth pattern Reviewed International journal

Soichiro Fushimi, Tetsuya Ogino, Ken Aoki, Junya Itakura, Toshihiro Ito, Tadashi Oeda, Hiroyuki Yanai, Akihiro Matsukawa

PATHOLOGY INTERNATIONAL   62 ( 1 )   69 - 71   2012.1

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DOI： 10.1111/j.1440-1827.2011.02741.x

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Correlation of neutrophil and monocyte derived interleukin-1 receptor antagonist and interleukin-8 with colitis severity in the rabbit Reviewed International journal

Kenta Kaneda, Fumio Saitoh, Hirom Shibusawa, Hidetaka Maegawa, Abbi R. Saniabadi, Nobuhito Kashiwagi, Akihiro Matsukawa

CYTOKINE   56 ( 2 )   508 - 514   2011.11

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Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

Activated neutrophils and monocytes produce interleukin (IL)-8, a pro-inflammatory chemokine, but also IL-1 receptor antagonist (IL-1ra), which is an anti-inflammatory cytokine. We were interested to see the profiles of IL-8 and IL-1ra in the colonic tissue and in the peripheral blood leukocytes (PBL) during the development of immune complex induced colitis in rabbits. IL-1ra and IL-8 in PBL were measured in 26 rabbits at time 0 h, 24 h, and 48 h after induction of colitis. The colons were removed at 48 h for measuring myeloperoxidase (MPO), ulcer area, IL-1ra and IL-8. Epithelial damage, crypt abscess formation and leukocyte infiltration of the colonic tissue were major features of this colitis model. During the development of colitis, there was an increase in circulating neutrophils and monocytes (P < 0.0001), but not lymphocytes. Likewise, elevated amounts of IL-Ira (P = 0.0001) and IL-8 (P = 0.0219) production by PBL were observed following induction of colitis. Flow cytometry revealed major source of IL-1ra was monocytes, while the main sources of IL-8 were neutrophils and monocytes. There was correlation between MPO and ulcer area (R(s) = 0.6327, P < 0.0001). At 24 h, PBL from MPO(High) group (n = 11) showed increased IL-1ra (P = 0.027) and IL-8 (P = 0.0128) levels vs MPO(Low) group (n = 15). IL-8 production by PBL showed correlation with tissue MPO (R(s) = 0.4273, P = 0.0295). The colitis in this model was associated with an increase in circulating monocytes and neutrophils, which released increased amounts of IL-8 and IL-1ra. Further, IL-8 and IL-1ra showed correlation with the severity of colitis. These observations should significantly further understandings on the role of neutrophils and monocytes in the immunopathogenesis of ulcerative colitis. (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.cyto.2011.07.008

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The Critical Role of Notch Ligand Delta-like 1 in the Pathogenesis of Influenza A Virus (H1N1) Infection Reviewed International journal

Toshihiro Ito, Ronald M. Allen, William F. Carson, Matthew Schaller, Karen A. Cavassani, Cory M. Hogaboam, Nicholas W. Lukacs, Akihiro Matsukawa, Steven L. Kunkel

PLOS PATHOGENS   7 ( 11 )   e1002341   2011.11

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Influenza A viral infections have been identified as the etiologic agents for historic pandemics, and contribute to the annual mortality associated with acute viral pneumonia. While both innate and acquired immunity are important in combating influenza virus infection, the mechanism connecting these arms of the immune system remains unknown. Recent data have indicated that the Notch system is an important bridge between antigen-presenting cells (APCs) and T cell communication circuits and plays a central role in driving the immune system to overcome disease. In the present study, we examine the role of Notch signaling during influenza H1N1 virus infection, focusing on APCs. We demonstrate here that macrophages, but not dendritic cells (DCs), increased Notch ligand Delta-like 1 (Dll1) expression following influenza virus challenge. Dll1 expression on macrophages was dependent on retinoic acid-inducible gene-I (RIG-I) induced type-I IFN pathway, and not on the TLR3-TRIF pathway. We also found that IFN alpha-Receptor knockout mice failed to induce Dll1 expression on lung macrophages and had enhanced mortality during influenza virus infection. Our results further showed that specific neutralization of Dll1 during influenza virus challenge induced higher mortality, impaired viral clearance, and decreased levels of IFN-gamma. In addition, we blocked Notch signaling by using gamma-secretase inhibitor (GSI), a Notch signaling inhibitor. Intranasal administration of GSI during influenza infection also led to higher mortality, and higher virus load with excessive inflammation and an impaired production of IFN-gamma in lungs. Moreover, Dll1 expression on macrophages specifically regulates IFN-gamma levels from CD4(+) and CD8(+) T cells, which are important for anti-viral immunity. Together, the results of this study show that Dll1 positively influences the development of anti-viral immunity, and may provide mechanistic approaches for modifying and controlling the immune response against influenza H1N1 virus infection.

DOI： 10.1371/journal.ppat.1002341

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黒色真菌Exophiala. jeanselmeiによる左手背皮下膿瘍を呈したフェオヒフォミコーシスの１例

森三郎, 平谷恵子, 井上さおり, 川上直明, 藤野寿幸, 松川昭博

尾道市立病院医学雑誌   27 ( 1 )   55 - 58   2011

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Language：Japanese   Publisher：尾道市立市民病院  

84歳女性。左手指示中手指関節背側の腫脹および発赤、圧痛、左手背部の軽度熱感を主訴に近医を受診後、著者らの施設へ紹介受診となった。左手指示中手指関節背側に対し皮化膿瘍部の穿刺吸引、排膿、ならびに患部切開排膿が施行された。その結果、、微生物的検査では糸状菌が、また培養検査では黒色真菌が検出された。更に加えて生育温度テストではExophiala jeanselmeiが同定された。尚、施行後は抗真菌薬の服用により左手背腫脹は軽減し、疼痛も消失した。

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Oxidative stress enhances granulocytic differentiation in HL 60 cells, an acute promyelocytic leukemia cell line. Reviewed International journal

Tetsuya Ogino, Michitaka Ozaki, Akihiro Matsukawa

Free radical research   44 ( 11 )   1328 - 1337   2010

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Language：English   Publishing type：Research paper (scientific journal)  

This paper studied the effects of physiologically available oxidants on HL 60 differentiation induced by all-trans retinoic acid (ATRA) or dimethyl sulfoxide (DMSO). Hydrogen peroxide (15 μM) and taurine chloramine (200 μM) induced HL 60 differentiation, which was detected by CD11b expression and superoxide production. Cd11b and p67phox mRNA expression was also augmented by these oxidants. In contrast, reducing chemicals, such as dithiothreitol, 2,3-dimercapto-1-propanol and N-acetylcysteine inhibited CD11b expression. Notably, DMSO inhibited methionine sulfoxide reductase activity, induced heme oxygenase-1 (ho-1) mRNA and enhanced oxidant-induced cell death, which indicated that DMSO intensified oxidative stress. After the addition of oxidants, ho-1 expression preceded the cd11b expression. Vicinal dithiol-reactive phenylarsine oxide (50 nM) also increased CD11b expression induced by DMSO or ATRA. These observations suggested that oxidative stress enhanced granulocytic differentiation of HL 60 cells and that leukaemic cell differentiation was affected by cellular redox status.

DOI： 10.3109/10715762.2010.503757

PubMed

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