[Negative regulatory factor of CAWS (Candida albicans water-soluble fraction) -vasculitis in CBA/J mice as assessed by comparison with Bruton's tyrosine kinase-deficient CBA/N mice].

Candida albicans water-soluble fraction (CAWS) has microbial pathogen-associated molecular patterns (PAMPs). It is a mannoprotein-β glucan complex obtained from the culture supernatant of Candida albicans NBRC1385 and 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 (Btk)-deficient CBA/N mice, which is a CAWS-vasculitis-sensitive strain having the same origin as CBA/J mice. After stimulation with various kinds of pathogen-associated molecular patterns (PAMPs), the production of inflammatory cytokines IL-6 and IFN-γwas induced in CBA/N mice, whereas that of immunosuppressive IL-10 was induced in CAWS-vasculitis-resistant CBA/J mice. The production of TIMP1, an endogenous matrix metalloproteinase (MMP) inhibitor, was observed in CBA/J mice. Furthermore, the induction of CAWS-vasculitis was inhibited by gene therapy using plasmid (pCAGGS-mIL-10). The results strongly suggest that the difference in the production of these cytokines is closely linked to the development of CAWS vasculitis.