Abstract
OK-432, a preparation of a low-virulence strain (Su) of Streptococcus pyogenes (Group A) killed by a penicillin and lyophilized, is a stiff inducer of Th1 cytokines, and exerts anti-cancer effects in tumor-bearing mice. OK-432 has been reported to consist of many bacterial components, such as peptidoglycan, M-protein, etc. However, it is yet to be ascertained which bacterial component induces T helper 1 (Th1) responses. For the last decade, Toll-like receptor (TLR) family proteins are well elucidated to play a role in recognizing bacterial components and inducing interleukin (IL)-12 from macrophages. Above all, peptidoglycan seems to be the agonist of TLR2 rather than the obverse. In our present study, the role of TLR2 for the recognition of OK-432 by macrophages and the effects of OK-432 are examined on murine allergic rhinitis model. Interestingly, results show IL-12 production by macrophages derived from TLR2 knock-out (ko) mice was significantly decreased, in comparison with that of macrophages derived from wild-type mice. Moreover, in TLR2 ko mice, no regulatory effect of OK-432 was observed on an allergic rhinitis model. These data indicate that TLR2 signaling is involved in regulating OK-432-induced anti-T helper 2 (Th2) immunity, and may offer a new prophylactic and therapeutic approach using OK-432 to downregulate allergic disorders, such as allergic rhinitis.
Highlights
The exact pathology of allergic rhinitis is well known to be an immediate type hypersensitivity connected with an expansion of T helper 2 (Th2) responses, including the production of allergen-specific immunoglobulin (Ig) E and nasal cavity infiltration of eosinophils [1,2,3,4,5]
Effect of OK-432 on IL-12 Production by Splenic Macrophages Derived from C3H/HeN, C3H/HeJ, TLR2
IL-12 production was significantly increased in the splenic cells stimulated by OK-432 derived from C3H/HeN mice as well as C3H/HeJ mice (Figure 1)
Summary
The exact pathology of allergic rhinitis is well known to be an immediate type hypersensitivity connected with an expansion of T helper 2 (Th2) responses, including the production of allergen-specific immunoglobulin (Ig) E and nasal cavity infiltration of eosinophils [1,2,3,4,5]. Allergic reaction can be allocated to two phases: systemic response at the induction phase and local allergic inflammation at the eliciting phase. Naive clusters of differentiation (CD) 4+ T cells initially stimulated with an allergen in the presence of interleukin (IL)-4 develop into CD4+ T cells, which secrete IL-4, IL-5, IL-6 and IL-13 for IgE isotype switching [6,7,8]. The allergic reaction is further promoted by the recruitment.
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