Lipopolysaccharide‐induced elevation and secretion of interleukin‐1β in the submandibular gland of male mice*

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Abstract
Summary: The intraperitoneal injection of lipopolysaccharide (LPS) (400 µg/kg body weight) induced the expression of mRNAs of inflammatory cytokines such as interleukin (IL)‐1β, IL‐6 and tumour necrosis factor (TNF)‐α 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– 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‐1β, 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‐1β 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‐1β 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‐1β 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‐1β, an inflammation cytokine, is induced and secreted into the saliva in response to endotoxin injected intraperitoneally.