Pathological Analysis of IL-18-dependently induced Atopic dermatitis mediated by Pattern Recognition Receptor Activation.

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 14021126
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Hyogo College of Medicine
• Principal Investigator: NAKANISHI Kenji Hyogo College of Medicine, Faculty pf Medicine, Professor, 教授 (60172350)
• Project Period (FY): 2002 – 2005
• Keywords: Allergy / Atooic Dermatitis / Innate Atonv / Th1 / IL-18

Research Abstract

We previously showed that transgenic mice that over-secrete IL-18 from their epidermal cells spontaneously develop AD-like dermatitis independently of Th2 or IgE response. Furthermore, recent clinical studies revealed that serum levels of IL-18 well parallel with the disease severity of AD. Therefore, we assumed that endogenous IL-18 contributes to the development of AD, particularly intrinsic AD. It is well documented that cutaneous infection with Staphylococcus aureus exacerbates clinical AD. Recently, we demonstrated that S. aureus -derived proteinA (SpA) induces IL-18 release from skin. Here, we generated a novel intrinsic AD mouse model by daily topical application of SpA following destroying skin barrier by detergent (SDS). AD-prone NC/Nga mice showed 100% development of AD and manifested skin phenotypes with dense accumulation of leukocytes including mast cells. They exhibited elevated serum levels of IL-18 but not IgE. After application of NC/Nga mice with SpA/SDS, CD4^+ T cells prepared from their regional lymph nodes produced IFN-γ, IL-3, IL-9 and IL-13. As they produce both Th1- and Th2-cytokines, we proposed to designate them super Th1 cell. Importantly, we found that IL-18 or IL-3 blockade, completely and partly, prevented the AD development by inhibiting this T cell differentiation or the mast cell accumulation, respectively. Thus, IL-18 might be a novel target for the treatment of infection-associated AD.

Research Products

• [Journal Article] Contribution of interleukin-18 to atopic dermatitis-like skin inflammation induced by Staphylococcus aureus product in mice. (2006)
  • Author(s): Terada, M
  • Journal Title: Proc. Natl. Acad. Sci. USA. Pages: 8816-8821
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Contribution of interleukin-18 to atopic dermatitis-like skininflammation induced by Staphylococcus aureus product in mice. (2006)
  • Author(s): Terada, M., Tsutsui, H., Imai, Y., Yasuda, K., Mizutani, H., Yamanishi, K., Kubo, M., Matsui, K., Sano, H., Nakanishi, K
  • Journal Title: Proc. Natl. Acad. Sci. USA. 103 Pages: 8816-8821
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Contribution of Toll-like receptor/myeloid diffferentiation factor 88 signallings to murine liver regeneration. (2005)
  • Author(s): Seki, E
  • Journal Title: Hepatology 41・3 Pages: 443-450
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A novel caspase-1/toll-like receptor 4-independent pathway of cell death induced by cytosolic Shigella in infected macrophages. (2005)
  • Author(s): Suzuki, T
  • Journal Title: J Biol Chem. 280・14 Pages: 14042-14050
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Endogenous interleukin-6 but not tumor necrosis factor-alpha, contributes to the development of toll-like receptor 4/myeloid differentiation factor 88-mediated acute arthritis in mice. (2005)
  • Author(s): Kyo, F
  • Journal Title: Arthritis Rheum 52・8 Pages: 2530-2540
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] IL-18 with IL-2 protects against Strongyloides venezuelensis infection by activating mucosal mast cell-dependent type 2 innate immunity. (2005)
  • Author(s): Sasaki, Y
  • Journal Title: J. Exp. Med. 202・5 Pages: 607-616
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Human anti-human IL-18 antibody recognizing the IL-18-binding site 3 with IL-18 Signaling blocking activity. (2005)
  • Author(s): Hamasaki, T
  • Journal Title: J. Biochem. 138・4 Pages: 433-442
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Contribution of Toll-like receptor/myeloid differentiation factor 88 signaling to murine liver regeneration. (2005)
  • Author(s): Seki, E., Tsutsui, H., Iimuro, Y., Naka, T., Son, G., Akira, S., Kishimoto, T., Nakanishi, K., Fujimoto, J.
  • Journal Title: Hepatology 41 Pages: 443-450
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A novel caspase-1/toll-like receptor 4-independent pathway of cell death induced by cytosolic Shigella in infected macrophages. (2005)
  • Author(s): Suzuki, T., Nakanishi, K., Tsutsui, H., Iwai, H., Akira, S., Inohara, N., Chamaillard, M., Nunez, U, Sasakawa, C.
  • Journal Title: J. Biol. Chem. 280 Pages: 14042-14050
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Endogenous IL-6 but not TNF-a contributes to the development of TLR4/MyD88-mediated acute arthritis in mice. (2005)
  • Author(s): Kyo, F., Futani, H., Matsui, K., Terada, M., Adachi, K., Nagata, K., Sano, H., Tateishi, H., Tsutsui, H., Nakanishi, K.
  • Journal Title: Arthritis ＆ Rheum. 52 Pages: 2530-2540
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] IL-18 with IL-2 protects against Strongyloides venezuelensis infection by activating mucosal mast cell-dependent type 2 innate immunity. (2005)
  • Author(s): Sasaki, Y., Yoshimoto, T., Maruyama, H., Tegoshi, T., Ohta, N., Arizono, N., Nakanishi.K.
  • Journal Title: J. Exp. Med. 202 Pages: 607-616
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Human anti-human IL-18 antibody recognizing the IL-18-binding site 3 with IL-18 signaling blocking activity. (2005)
  • Author(s): Hamasaki, T., Hashiguchi, S., Ito, Y., Kato, Z., Nakanishi, K., Nakashima, T., Sugimura, K.
  • Journal Title: J. Biochem. 138 Pages: 433-442
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] IL-18とアトピーモデル (2005)
  • Author(s): 善本知広
  • Total Pages: 380
  • Publisher: Molecular Medicine
  • Description: 「研究成果報告書概要(和文)」より