ORIGINAL ARTICLE: Lipopolysaccharide-induced elevation and secretion of interleukin-1 beta in the submandibular gland of male mice

The intraperitoneal injection of lipopolysaccharide (LPS) (400 mu g-kg body weight) induced the expression of mRNAs of inflammatory cytokines such as interleukin (IL)-1 beta , IL-6 and tumour necrosis factor (TNF)- alpha in the submandibular gland (SMG) of C3H-HeN mice but not that of C3H-HeJ mice, a mutant strain for Toll-like receptor-4 (TLR-4 super(-) mutant). The mRNA levels of these cytokines in the SMG of the wild-type mice increased as early as 3 hr after injection, peaked at 3-6 hr, and had decreased again by 24 hr. In this study, we particularly focused on IL-1 beta , and induction by this endotoxin was investigated in detail. Denervation of the superior cervical trunk and chorda tympani nerve did not diminish the LPS-induced elevation of IL-1 beta mRNA in the SMG, indicating the irrelevance of the central nervous system in this induction. TLR-4 mRNA and protein were shown to be strongly expressed in the SMG, suggesting the direct action of LPS on this gland. IL-1 beta proteins were localized in the secretory granules of granular convoluted tubular (GCT) cells, and their molecular weights in the gland were 17.5 and 20 kDa. IL-1 beta of the same size appeared in the saliva 6 hr after LPS injection in C3H-HeN but not in C3H-HeJ mice. The present study thus suggests that IL-1 beta , an inflammation cytokine, is induced and secreted into the saliva in response to endotoxin injected intraperitoneally.