顎下腺における炎症性サイトカインIL-βのプロセッシング(高田充歯科基礎医学奨励賞受賞講演)
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概要
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We have shown earlier that the expression of interleukin-1β (IL-1β) mRNA is increased in the submandibular gland (SMG) after injection of lipopolysaccharide (LPS). In this present study we suggest that tissue kallikrein mK13 is a candidate of the processing enzyme for the precursor of IL-1β (pro-IL-1β) in the SMG. High levels of 17.5- and 20-kDa IL-1β proteins were detected by Western blotting in the SMG, and saliva from LPS-injected mice. Despite this fact, pro-IL-1β with a molecular size of 35-kDa was not detected in this tissue. The protein for IL-1β-converting enzyme (ICE) was expressed only at a low level in the SMG as compared with its level in various epithelial tissues or LPS-stimulated macrophages. We detected the strong expression of members of kallikrein family (mK1, mK9, mK13, and mK22) in the SMG but not other tissues. By incubation with mK13, but not with mK1, mK9, nor mK22, the 35-kDa pro-IL-1β was cleaved to give two major products with molecular masses of 17.5- and 22- kDa, which production was inhibited by PMSF, a serine protease inhibitor, but not by ICE inhibitors. The pro-IL-β peptide segment, which includes the putative processing site, was hydrolyzed at Leu^<113> and Leu^<114> by incubation with mK13. The immunohistochemistry and an autonomic therapy experiment showed that IL-1β and kallikrein mK13 were co-localized in the secretory granules of granular convoluted tubular cells. Our present results thus suggest that kallikrein mK13 is a plausible candidate for the processing enzyme for pro-IL-1β in the SMG of mice.
- 徳島大学の論文