Functional effects of IL-33 on skin tissue cells

• Project/Area Number: 23591666
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: MATSUDA Akio 独立行政法人国立成育医療研究センター, 免疫アレルギー研究部, 室長 (10359705)
• Co-Investigator(Kenkyū-buntansha): FUTAMURA Kyoko 独立行政法人国立成育医療研究センター, 免疫アレルギー研究部, 研究員 (60596956)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: IL-33 / 皮膚組織細胞 / 皮膚炎症

Research Abstract

The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of barrier tissue cells such as epithelial cells and endothelial cells. IL-33 passively released from damaged tissue has been shown to be acted as a cytokine. We found that IL-33 can act on epidermal keratinocytes and dermal microvascular endothelial cells to induce neutrophil-associated cytokine/chemokine productions.
Furthermore, we have established an in vitro scratch model of skin tissue cells, and found that keratinocyte extracts contained unidentified pro-inflammatory substances to mediate inflammatory responses to intact cultured skin tissue cells such as fibroblasts and microvascular endothelial cells. These findings suggest the existence of a molecular machinery of "itch-scratch cycle" in the inflammatory skin diseases such as atopic dermatitis.

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 Volume: (in press) Issue: 3 Pages: 344-353
  • 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 Issue: 1 Pages: e86106-e86106
  • DOI: 10.1371/journal.pone.0086106
  • Peer Reviewed
• [Journal Article] Cell type-dependent effects of corticosteroid on periostin production by primary human tissue cells (2013)
  • Author(s): Shoda, T., K. Futamura, F. Kobayashi, H. Saito, K. Matsumoto, and A. Matsuda
  • Journal Title: Allergy Volume: 68(11) Issue: 11 Pages: 1467-1470
  • DOI: 10.1111/all.12240
  • Peer Reviewed
• [Journal Article] Gastrointestinal Food Allergy in Infants (2013)
  • Author(s): Morita, H., I. Nomura, A. Matsuda, H. Saito, and K. Matsumoto
  • Journal Title: Allergology International Volume: 62 Issue: 3 Pages: 297-307
  • DOI: 10.2332/allergolint.13-RA-0542
  • NAID: 130004477199
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Salivary cortisol response to stress in young children with atopic dermatitis. (2013)
  • Author(s): Kojima R, Matsuda A, Nomura I, Matsubara O, Nonoyama S, Ohya Y, Saito H, Matsumoto K.
  • Journal Title: Pediatr Dermatol. Volume: 30 Issue: 1 Pages: 17-22
  • DOI: 10.1111/j.1525-1470.2012.01770.x
  • Peer Reviewed
• [Journal Article] Factors Associated with Steroid Phobia in Caregivers of Children with Atopic Dermatitis. (2013)
  • Author(s): Kojima R, Fujiwara T, Matsuda A, Narita M, Matsubara O, Nonoyama S, Ohya Y, Saito H, Matsumoto K.
  • Journal Title: Pediatr Dermatol. Volume: 30 Issue: 1 Pages: 29-35
  • DOI: 10.1111/j.1525-1470.2012.01808.x
  • Peer Reviewed
• [Journal Article] 川崎病における治療反応性とバイオマーカー (2013)
  • Author(s): 阿部淳, 松田明生
  • Journal Title: 日本臨床免疫学会会誌 Volume: vol. 36 (1) Pages: 27-34
  • NAID: 10031157132
• [Journal Article] IL-33とアレルギー(特集アレルギーの発症とサイトカイン) (2013)
  • Author(s): 大保木啓介, 松田明生, 松本健治
  • Journal Title: 臨床免疫・アレルギー科 Volume: 60巻1号 Pages: 20-27
  • NAID: 40019751840
• [Journal Article] 炎症性皮膚疾患とIL-33(特集疾患の発症とサイトカイン) (2013)
  • Author(s): 二村恭子, 松田明生
  • Journal Title: 臨床免疫・アレルギー科 Volume: 60巻4号 Pages: 357-362
  • NAID: 40019836816
• [Journal Article] IL-33とアレルギー (2013)
  • Author(s): 大保木啓介、松田明生、松本健治
  • Journal Title: 臨床免疫・アレルギー科 Volume: 60 Pages: 20-27
• [Journal Article] 炎症性皮膚疾患とIL-33 (2013)
  • Author(s): 二村恭子、松田明生
  • Journal Title: 臨床免疫・アレルギー科 Volume: 60 Pages: 357-362
• [Journal Article] Antigen-specific T-cell responses in patients with non-IgE-mediated gastrointestinal food allergy are predominantly skewed to T(H)2. (2012)
  • Author(s): Morita H, Nomura I, Orihara K, Yoshida K, Akasawa A, Tachimoto H, Ohtsuka Y, Namai Y, Futamura M, Shoda T, Matsuda A, Kamemura N, Kido H, Takahashi T, Ohya Y, Saito H, Matsumoto K.
  • Journal Title: J Allergy Clin Immunol. Volume: 131 Issue: 2 Pages: 590-2
  • DOI: 10.1016/j.jaci.2012.09.005
  • Peer Reviewed
• [Journal Article] ST2 Requires Th2-, but Not Th17-, Type Airway Inflammation in Epicutaneously Antigen-Sensitized Mice (2012)
  • Author(s): Morita H, Arae K, Ohno T, Kajiwara N, Oboki, K, Matsuda A, Suto H, Okumura K, Sudo K, Takahashi T, Matsumoto K, Nakae, S
  • Journal Title: Allergology International Volume: 61 Issue: 2 Pages: 265-273
  • DOI: 10.2332/allergolint.11-OA-0379
  • NAID: 130004477129
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Anti-inflammatory effects of high-dose IgG on TNF-α-activated human coronary artery endothelial cells. (2012)
  • Author(s): Matsuda A, Morita H, Unno H, Saito H, Matsumoto K, Hirao Y, Munechika K, Abe J
  • Journal Title: Eur J Immunol. Volume: 42 Issue: 8 Pages: 2121-31
  • DOI: 10.1002/eji.201242398
  • Peer Reviewed
• [Journal Article] 気道リモデリングと微小血管病変
  • Author(s): 松田明生
  • Journal Title: 日本胸部臨床2012第71巻増刊号非腫瘍性気道病変のすべて
• [Presentation] Comprehensive analysis of offending milk protein components in non-IgE-mediated gastrointestinal food allergens by antigen-specific lymphocyte proliferation test (2014)
  • Author(s): Shoda T, Nomura I, Morita H, Matsuda A, Saito H, Matsumoto K
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2014-05-10
• [Presentation] 重症アレルギー性眼疾患患者の涙液におけるサイトカインプロファイル解析 (2014)
  • Author(s): 岡田直子、藤島浩、深川和己、松田明生、斎藤博久、松本健治
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2014-05-10
• [Presentation] ORMDL3遺伝子発現レベルの気道上皮細胞におけるTSLP産生に対する影響 (2014)
  • Author(s): 二村恭子、松田明生、斎藤博久、松本健治
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2014-05-10
• [Presentation] 肺微小血管内皮細胞におけるIL-33発現増強機構 (2014)
  • Author(s): 杉江真以子、正田哲雄、斎藤博久、松本健治、松田明生
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2014-05-09
• [Presentation] 血小板は恒常的に活性型IL-33蛋白を発現する (2014)
  • Author(s): 竹田知広、海野浩寿、森田英明、斎藤博久、松本健治、松田明生
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2014-05-09
• [Presentation] 新生児-乳児消化管アレルギー、クラスター3における、血清IL-33,TSLPの上昇 (2014)
  • Author(s): 野村伊知郎、正田哲雄、松田明生、森田英明、新井勝大、清水泰岳、山田佳之、成田雅美、大矢幸弘、斎藤博久、松本健治
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2014-05-09
• [Presentation] Interleukin-33 and thymic stromal lymphopoietin are preferentially elevated in the sera of infants with eosinophilic gastroenteritis (2014)
  • Author(s): Nomura I, Matsuda A, Shoda T, Morita H, Arai K, Shimizu H, Yamada Y, Ohya Y, Saito H, Matsumoto K
  • Organizer: Annual meeting of the American Academy of Allergy, Asthma and Immunology
  • Place of Presentation: San Diego, CA
  • Year and Date: 2014-03-04
• [Presentation] Comprehensive analysis of offending milk protein components in non-IgE-mediated gastrointestinal food allergies by antigen-specific lymphocyte proliferation test (2014)
  • Author(s): Shoda T, Nomura I, Morita H, Matsuda A, Saito H, Matsumoto K
  • Organizer: Annual meeting of the American Academy of Allergy, Asthma and Immunology
  • Place of Presentation: San Diego, CA
  • Year and Date: 2014-03-04
• [Presentation] Cytokine secretion profiles in the tears of patients with chronic allergic conjunctivitis (2014)
  • Author(s): Okada N, Fujishima H, Fukagawa K, Matsuda A, Saito H, Matsumoto K
  • Organizer: Annual meeting of the American Academy of Allergy, Asthma and Immunology
  • Place of Presentation: San Diego, CA
  • Year and Date: 2014-03-04
• [Presentation] Platelets constitutively express Interleukin-33 protein (2014)
  • Author(s): Takeda T, Unno H, Morita H, Saito H, Matsumoto K, Matsuda A
  • Organizer: Annual meeting of the American Academy of Allergy, Asthma and Immunology
  • Place of Presentation: San Diego, CA
  • Year and Date: 2014-03-04
• [Presentation] Exposure of mice to silica crystals and poly I : C synergistically enhances neutrophil infiltration and epithelial damage in the airway (2014)
  • Author(s): Unno H, Morita H, Saito H, Matsumoto K, Matsuda A
  • Organizer: Annual meeting of the American Academy of Allergy, Asthma and Immunology
  • Place of Presentation: San Diego, CA
  • Year and Date: 2014-03-02
• [Presentation] IL-17 enhances TNF-α-induced, but not IL-1β-induced, expression of neutrophil-associated cytokines by human lung tissue cells (2014)
  • Author(s): Matsuda A, Motomura K, Shoda T, Futamura K, Saito H, Matsumoto K
  • Organizer: Annual meeting of the American Academy of Allergy, Asthma and Immunology
  • Place of Presentation: San Diego, CA
  • Year and Date: 2014-03-01
• [Presentation] 肺の組織構成細胞におけるペリオスチン産生とステロイド剤の効果 (2013)
  • Author(s): 正田哲雄、二村恭子、斎藤博久、松本健治、松田明生
  • Organizer: 第63回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京、ホテルニューオータニ (第10回日本アレルギー学会学術大会賞受賞)
  • Year and Date: 2013-11-30
• [Presentation] 新生児-乳児消化管アレルギー、オンライン登録システムの解析 (2013)
  • Author(s): 野村伊知郎、森田英明、正田哲雄、松田明生、山田佳之、大塚宜一、新井勝大、大矢幸弘、斎藤博久、松本健治
  • Organizer: 第50回日本小児アレルギー学会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2013-10-20
• [Presentation] クラゲ摂食後にアナフィラキシーショックを生じた14歳男児 (2013)
  • Author(s): 大久保祐輔、吉田幸一、榊原裕史、寺川敏郎、佐々木真利、古川真弓、正田哲雄、松田明生、松本健治、赤澤晃
  • Organizer: 第50回日本小児アレルギー学会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2013-10-20
• [Presentation] 真皮細胞によるペリオスチン産生に対するステロイド薬の効果 (2013)
  • Author(s): 正田哲雄、二村恭子、斎藤博久、松本健治、松田明生
  • Organizer: 第50回日本小児アレルギー学会
  • Place of Presentation: 横浜、パシフィコ横浜 (第50回日本小児アレルギー学会ベストポスター賞受賞)
  • Year and Date: 2013-10-20
• [Presentation] Anti-inflammatory effects of high-dose IgG on TNF-α, but not IL-1β-activated human coronary artery endothelial cells (2013)
  • Author(s): Matsuda A, Morita H, Unno H, Motomura K, Saito H, Matsumoto K, Abe J
  • Organizer: 15^<th> International Congress of Immunology
  • Place of Presentation: Milan, Italy
  • Year and Date: 2013-08-23
• [Presentation] 皮膚構成細胞におけるTARC産生に関する研究 (2013)
  • Author(s): 二村恭子、正田哲雄、本村健一郎、吉岡莉紗、松本健治、松田明生
  • Organizer: 第112回日本皮膚科学会総会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2013-06-14
• [Presentation] 新生児・乳児消化管アレルギーの発症日令、4つのクラスター及び欧米との差 (2013)
  • Author(s): 野村伊知郎、森田英明、新井勝大、松田明生、成田雅美、大矢幸弘、斎藤博久、松本健治
  • Organizer: 第25回日本アレルギー学会春季臨床大会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2013-05-12
• [Presentation] 皮膚構成細胞からのTARC産生に関する検討 (2013)
  • Author(s): 正田哲雄、二村恭子、斎藤博久、松本健治、松田明生
  • Organizer: 第25回日本アレルギー学会春季臨床大会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2013-05-12
• [Presentation] アトピー性皮膚炎患児の養育者におけるステロイド忌避の予測因子についての検討 (2013)
  • Author(s): 小島令嗣、藤原武男、松田明生、成田雅美、大矢幸弘、斎藤博久、松本健治
  • Organizer: 第25回日本アレルギー学会春季臨床大会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2013-05-12
• [Presentation] 結晶シリカとpoly I : Cのマウスへの吸入暴露は好中球性気道炎症を増悪させる (2013)
  • Author(s): 海野浩寿、森田英明、新江賢、中江進、斎藤博久、松本健治、松田明生
  • Organizer: 第25回日本アレルギー学会春季臨床大会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2013-05-12
• [Presentation] 気道組織細胞におけるIL-17の作用 (2013)
  • Author(s): 松田明生、二村恭子、正田哲雄、斎藤博久、松本健治
  • Organizer: 第25回日本アレルギー学会春季臨床大会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2013-05-12
• [Presentation] Infants with food protein-induced enterocolitis syndrome (FPIES) can be classified into two distinct subgroups based on the presence or absence of bloody stool and their antigen-specific cytokine production profiles (2013)
  • Author(s): Morita H, Nomura I, Shoda T, Unno H, Matsuda A, Saito H, Matsumoto K
  • Organizer: Annual meeting of the American Academy of Allergy, Asthma and Immunology
  • Place of Presentation: San Antonio, TX
  • Year and Date: 2013-02-25
• [Presentation] Distinct differences between cluster 3 and 4 of non-IgE-mediated gastrointestinal allergy in allergen-specific lymphocyte proliferation test and histological findings of the GI mucosa (2013)
  • Author(s): Nomura I, Morita H, Shoda T, Morita K, Matsuda A, Shimizu H, Arai K, Nakazawa A, Ohya Y, Saito H, Matsumoto K
  • Organizer: Annual meeting of the American Academy of Allergy, Asthma and Immunology
  • Place of Presentation: San Antonio, TX
  • Year and Date: 2013-02-25
• [Presentation] Cytokine-stimulated human dermal microvascular endothelial cells and fibroblasts produce thymus and activation-regulated chemokine (TARC) (2013)
  • Author(s): Shoda T, Futamura K, Motomura K, Saito H, Matsumoto K, Matsuda A
  • Organizer: Annual meeting of the American Academy of Allergy, Asthma and Immunology
  • Place of Presentation: San Antonio, TX
  • Year and Date: 2013-02-25
• [Presentation] Exposure to silica crystals and poly (I : C) induces caspase-dependent apoptosis of human bronchial epithelial cells (2013)
  • Author(s): Unno H, Futamura K, Kojima R, Morita H, Saito H, Matsumoto K, Matsuda A
  • Organizer: Annual meeting of the American Academy of Allergy, Asthma and Immunology
  • Place of Presentation: San Antonio, TX
  • Year and Date: 2013-02-25
• [Presentation] 免疫グロブリンによる冠動脈血管内皮細胞の抗炎症効果 (2013)
  • Author(s): 松田明生、森田英明、海野浩寿、斎藤博久、松本健治、阿部淳
  • Organizer: 第62回日本アレルギー学会秋季学術大会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2013-02-25
• [Presentation] High-dose IgG completely inhibited TNF-α-induced, but not IL-1βor poly (I : C)-induced, G-CSF expression by human coronary artery endothelial cells (2013)
  • Author(s): Matsuda A, Morita H, Unno H, Saito H, Matsumoto K, Abe J
  • Organizer: Annual meeting of the American Academy of Allergy, Asthma and Immunology
  • Place of Presentation: San Antonio, TX
  • Year and Date: 2013-02-23
• [Presentation] 皮膚構成細胞からのTARC産生に関する検討 (2013)
  • Author(s): 正田哲雄、二村恭子、斎藤博久、松本健治、松田明生
  • Organizer: 第25回日本アレルギー学会春季臨床大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] アトピー性皮膚炎患児の養育者におけるステロイド忌避の予測因子についての検討 (2013)
  • Author(s): 小島令嗣、藤原武男、松田明生、成田雅美、大矢幸弘、斎藤博久、松本健治
  • Organizer: 第25回日本アレルギー学会春季臨床大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 結晶シリカとpoly I:Cのマウスへの吸入暴露は好中球性気道炎症を増悪させる (2013)
  • Author(s): 海野浩寿、森田英明、新江賢、中江進、斎藤博久、松本健治、松田明生
  • Organizer: 第25回日本アレルギー学会春季臨床大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 気道組織細胞におけるIL-17の作用 (2013)
  • Author(s): 松田明生、二村恭子、正田哲雄、斎藤博久、松本健治
  • Organizer: 第25回日本アレルギー学会春季臨床大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 肺の組織構成細胞におけるペリオスチン産生とステロイド剤の効果 (2013)
  • Author(s): 正田哲雄、二村恭子、斎藤博久、松本健治、松田明生
  • Organizer: 第63回日本アレルギー学会秋季学術大会
  • Place of Presentation: ホテルニューオータニ
• [Presentation] 培養皮膚3次元モデルに対するIL-33の作用 (2012)
  • Author(s): 二村恭子、正田哲雄、海野浩寿、斎藤博久、松本健治、松田明生
  • Organizer: 第62回日本アレルギー学会秋季学術大会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2012-11-30
• [Presentation] 結晶シリカはpoly I : C共存下でカスパーゼを介した気道上皮細胞のアポトーシスを誘導する (2012)
  • Author(s): 海野浩寿、二村恭子、小島令嗣、森田英明、斎藤博久、松本健治、松田明生
  • Organizer: 第62回日本アレルギー学会秋季学術大会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2012-11-30
• [Presentation] 新生児・乳児消化管アレルギー、クラスター1,2におけるリンパ球刺激試験、サイトカイン産生の差 (2012)
  • Author(s): 野村伊知郎、森田英明、正田哲雄、大矢幸弘、松田明生、斎藤博久、松本健治
  • Organizer: 第62回日本アレルギー学会秋季学術大会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2012-11-29
• [Presentation] Silica crystals cause cellular damage in TLR3-activated human bronchial epithelial cells (2012)
  • Author(s): Matsuda A, Unno H, Futamura K, Kojima R, Morita H, Matsumoto K, Saito H
  • Organizer: 29^<th> Symposium of Collegium Internationale Allergologicum
  • Place of Presentation: Teju Island, Korea
  • Year and Date: 2012-10-15
• [Presentation] 培養皮膚3次元モデルに対するIl-33の作用 (2012)
  • Author(s): 二村恭子、正田哲雄、海野浩寿、斎藤博久、松本健治、松田明生
  • Organizer: 第62回日本アレルギー学会秋季学術大会
  • Place of Presentation: 大阪
• [Presentation] 皮膚構成細胞に対するIL-33の作用 (2012)
  • Author(s): 二村恭子、海野浩寿、斎藤博久、松本健治、松田明生
  • Organizer: 第24回日本アレルギー学会春季学術大会
  • Place of Presentation: 大阪