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* Laboratory for Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan;
Laboratory of Genetic Resources, National Institute of Biomedical Innovation, Osaka, Japan;
National Institute of Infectious Diseases, Tokyo, Japan; and
Graduate School of Medicine and School of Medicine, Chiba University, Chiba, Japan
Candida albicans water-soluble fraction (CAWS), a mannoprotein-β-glucan complex obtained from the culture supernatant of C. albicans NBRC1385, exhibits vasculitis-inducing activity (CAWS-vasculitis) in mice. The sensitivity to CAWS-vasculitis varies greatly among mouse strains. This study examined the factors contributing to or inhibiting CAWS-vasculitis using CAWS-vasculitis-resistant CBA/J mice and Bruton’s tyrosine kinase-deficient CBA/N mice, which is a CAWS-vasculitis-sensitive strain that has the same origin as CBA/J mice. After stimulation with various kinds of pathogen-associated molecular patterns, the production of inflammatory cytokines IL-6 and IFN-
was induced in CBA/N mice, whereas that of immunosuppressive IL-10 was induced in CAWS-vasculitis-resistant CBA/J mice. Furthermore, the production of tissue inhibitor of metalloproteinase 1, an endogenous matrix metalloproteinase inhibitor, was observed in CBA/J mice. The results strongly suggest that the difference in the production of these cytokines is closely linked to the development of CAWS-vasculitis.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was partly supported by a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Promotion and Mutual Aid Corporation for Private Schools (Japan). This study was also supported by the Ministry of Health, Labour, and Welfare of Japan by a Grant for "Research on Regulatory Science of Pharmaceuticals and Medical Devices" and by the Program for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry.
2 Address correspondence and reprint requests to Dr. Naohito Ohno, Laboratory for Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. E-mail address: ohnonao{at}ps.toyaku.ac.jp
3 Abbreviations used in this paper: CAWS, Candida albicans water-soluble fraction; Btk, Bruton’s tyrosine kinase; EVG, Elastica-van-Gieson; MMP, matrix metalloprotease; PAF, platelet-activating factor; PAMP, pathogen-associated molecular pattern; TIMP1, tissue inhibitor of metalloproteinase 1.
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