Pathogenesis and mechanisms of protease antigen-induced innate-type airway inflammation

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390262
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: MATSUMOTO Kenji 独立行政法人国立成育医療研究センター, その他部局等, その他 (60181765)
• Co-Investigator(Kenkyū-buntansha): SAITO Hirohisa 独立行政法人国立成育医療研究センター, 研究所免疫アレルギー研究部, 副所長 (40130166) ; NAKAE Susumu 東京大学医科学研究所システム疾患モデル研究センター, システムズバイオロジー研究分野, 准教授 (60450409) ; OOBOKI Keisuke 独立行政法人国立成育医療研究センター, 研究所免疫アレルギー研究部, 上級研究員 (80415108)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: IL-33 / プロテアーゼ / アレルギー・ぜんそく

Research Abstract

After inhalation of papain (mimic of allergen with protease activity), we found 1. Early reaction (1 day) with neutrophil-dominant inflammation was induced by IL-33-release via activation of non-T cells, whereas late reaction (7 days) with eosinophil-dominant inflammation was induced by IL-33-release via activation of rag-2+ cells. 2. Biphasic (6h and 72 h) IL-13 induction was observed after IL-33 release which peaks at 6h after inhalation. 3. Immune response against papain varied with gender, age and strain. These findings may help understanding the development and pathogenesis of bronchial asthma.

Research Products

• [Journal Article] Silica and Double-Stranded RNA Synergistically Induce Bronchial Epithelial Apoptosis and Airway Inflammation (2014)
  • Author(s): Unno H, Futamura K, Morita H, Kojima R, Arae K, Nakae S, Ida H, Saito H, Matsumoto K, Matsuda A
  • Journal Title: Am J Respir Cell Mol Biol
  • DOI: 10.1165/rcmb.2013-0281OC
  • Peer Reviewed
• [Journal Article] Galectin-9 enhances cytokine secretion, but suppresses survival and degranulation, in human mast cell line (2014)
  • Author(s): Kojima R, Ohno T, Iikura M, Niki T, Hirashima M, Iwaya K, Tsuda H, Nonoyama S, Matsuda A, Saito H, Matsumoto K, Nakae S
  • Journal Title: PLoS ONE Volume: 9 Pages: e86106
  • DOI: 10.1371/journal.pone.0086106
  • Peer Reviewed
• [Journal Article] GATA-1 regulates the generation and function of basophils (2013)
  • Author(s): Nei Y, Obata-Ninomiya K, Tsutsui H, Ishiwata K, Miyasaka M, Matsumoto K, Nakae S, Kanuka H, Inase N, Karasuyama H
  • Journal Title: Proc Natl Acad Sci USA Volume: 110 Pages: 18620-5
  • DOI: 10.1073/pnas.1311668110
  • Peer Reviewed
• [Journal Article] IL-33, but not IL-25, is crucial for the development of house dust mite antigen-induced allergic rhinitis (2013)
  • Author(s): Nakanishi W, Yamaguchi S, Matsuda A, Suzukawa M, Shibui A, Nambu A, Kondo K, Suto H, Saito H, Matsumoto K, Yamasoba T, Nakae S
  • Journal Title: PLoS ONE Volume: 8 Pages: e78099
  • DOI: 10.1371/journal.pone.0078099
  • Peer Reviewed
• [Journal Article] Role of interleukin-33 in innate-type immune cells in allergy (2013)
  • Author(s): Nakae S, Morita H, Ohno T, Arae K, Matsumoto K, Saito H
  • Journal Title: Allergol Int Volume: 62 Pages: 13-20
  • DOI: 10.2332/allergolint.13-RAI-0538
  • Peer Reviewed
• [Journal Article] Role of IL-25 and IL-33 in allergic diseases (2013)
  • Author(s): Morita H, Unno H, Arae K, Ohno T, Saito H, Matsumoto K, Nakae S
  • Journal Title: Arerugi Volume: 62 Pages: 924-35
  • Peer Reviewed
• [Journal Article] Epithelial cell-derived IL-25, but not Th17 cell-derived IL-17 or IL-17F, is crucial for murine asthma (2012)
  • Author(s): Suzukawa M, Morita H, Nambu A, Arae K, Shimura E, Shibui A, Yamaguchi S, Suzukawa K, Nakanishi W, Oboki K, Kajiwara N, Ohno T, Ishii A, Korner H, Cua DJ, Suto H, Yoshimoto T, Iwakura Y, Yamasoba T, Ohta K, Sudo K, Saito H, Okumura K, Broide DH, Matsumoto K, Nakae S
  • Journal Title: J Immunol Volume: 189 Pages: 3641-52
  • DOI: 10.4049/jimmunol.1200461
• [Journal Article] Histamine-releasing factor has a proinflammatory role in mouse models of asthma and allergy (2012)
  • Author(s): Kashiwakura JC, Ando T, Matsumoto K, Kimura M, Kitaura J, Matho MH, Zajonc DM, Ozeki T, Ra C, MacDonald SM, Siraganian RP, Broide DH, Kawakami Y, Kawakami T
  • Journal Title: J Clin Invest Volume: 122 Pages: 218-28
  • DOI: 10.1172/jci59072
• [Journal Article] The alarmin interleukin-33 drives protective antiviral CD8 + T cell responses (2012)
  • Author(s): Bonilla WV, Fröhlich A, Senn K, Kallert S, Fernandez M, Johnson S, Kreutzfeldt M, Hegazy AN, Schrick C, Fallon PG, Klemenz R, Nakae S, Adler H, Merkler D, Löhning M, Pinschewer DD
  • Journal Title: Science Volume: 335(6071) Pages: 984-989
  • DOI: 10.1126/science.1215418
  • Peer Reviewed
• [Journal Article] Role of mast cells and basophils in IgE responses and in allergic airway hyperresponsiveness (2012)
  • Author(s): Sawaguchi M, Tanaka S, Nakatani Y, Harada Y, Mukai K, Matsunaga Y, Ishiwata K, Oboki K, Kambayashi T, Watanabe N, Karasuyama H, Nakae S, Inoue H, Kubo M
  • Journal Title: J Immunol Volume: 188 Pages: 1809-1818
  • DOI: 10.4049/jimmunol.1101746
  • Peer Reviewed
• [Journal Article] Paracrine IL-33 stimulation enhances lipopolysaccharide-mediated macrophage activation (2011)
  • Author(s): Ohno T, Oboki K, Morita H, Kajiwara N, Arae K, Tanaka S, Ikeda M, Iikura M, Akiyama T, Inoue J, Matsumoto K, Sudo K, Azuma M, Okumura K, Kamradt T, Saito H, Nakae S
  • Journal Title: PLoS ONE Volume: 6 Pages: e18404
  • DOI: 10.1371/journal.pone.0018404
• [Journal Article] IL-33 and airway inflammation (2011)
  • Author(s): Oboki K, Nakae S, Matsumoto K, Saito H
  • Journal Title: Allergy Asthma Immunol Res Volume: 3 Pages: 81-8
  • DOI: 10.4168/aair.2011.3.2.81
• [Journal Article] Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations (2011)
  • Author(s): Noguchi E, Sakamoto H, Hirota T, Ochiai K, Imoto Y, Sakashita M, Kurosaka F, Akasawa A, Yoshihara S, Kanno N, Yamada Y, Shimojo N, Kohno Y, Suzuki Y, Kang MJ, Kwon JW, Hong SJ, Inoue K, Goto Y, Yamashita F, Asada T, Hirose H, Saito I, Fujieda S, Hizawa N, Sakamoto T, Masuko H, Nakamura Y, Nomura I, Tamari M, Arinami T, Yoshida T, Saito H, Matsumoto K
  • Journal Title: PLoS Genet Volume: 7 Pages: e1002170
  • DOI: 10.1371/journal.pgen.1002170
• [Journal Article] Peripheral blood mononuclear cells from patients with bronchial asthma show impaired innate immune responses to rhinovirus in vitro (2011)
  • Author(s): Iikura K, Katsunuma T, Saika S, Saito S, Ichinohe S, Ida H, Saito H, Matsumoto K
  • Journal Title: Int Arch Allergy Immunol Volume: 155 Pages: 27-33
  • DOI: 10.1159/000327262
• [Journal Article] Cimetidine Enhances Antigen-Specific IgE and Th2 Cytokine Production (2011)
  • Author(s): Arae K, Oboki K, Ohno T, Hirata M, Nakae S, Taguchi H, Saito H, Nakajima T
  • Journal Title: Allergol Int Volume: 60 Pages: 339-344
  • DOI: 10.2332/allergolint.10-OA-0255
  • Peer Reviewed