Local immune tolerance via Toll-like receptor 2 and 4 in the bovine oviduct epithelial cells

抄録

Oviduct is the venue for fertilization and faced to sperm and pathogens in physiological and pathophysiological modes, respectively.These allogenic factors may induce female immunity. Little is known about mechanisms for local immune tolerance in the oviduct. Toll-like receptors (TLRs) are involved in innate immune response to microbial pathogens and also contribute to recognition of endogenous molecules derived from physiological processes. We aimed to investigate local regulation of immunity in the oviduct using bovine oviduct epithelial cell (BOEC) culture. A low dose of lipopolysaccharide (LPS, 10 ng/ml) up-regulated TLR-4,COX2, and IL1b (Th1 cytokine) mRNA expression, toward inflammatory mode. In contrast, a high dose of LPS (100 ng/ml) up-regulated TLR-2, IL1b, and IL4 (Th2 cytokine), but not TLR-4, mRNA expression, toward the suppression of inflammation. Co-stimulation of BOEC by LPS and sex hormones at concentrations observed during preovulatory period in situ (E2, 1ng/ml; P4, 1 ng/ml; LH, 10 ng/ml) completely blocked the stimulatory effects of LPS. In physiological model, LH substantially stimulated TLR2 and IL4 mRNA expression, toward immune tolerance. A stimulation with LH, P4, E2, or all together (LH+P4+E2) up-regulated IL4 and down-regulated IL1b mRNA expression, suggesting the shift of balance of Th cytokines toward Th2 type. Taken together,the bovine oviduct is quite sensitive to low levels of LPS in pro-inflammatory response, but higher level of LPS induces anti-inflammatory response to avoid harmful over-reactions; besides LH has a critical role in the induction of immune tolerance in the bovine oviduct