Inflammation by mast cell kininogen and its suppression -Development of a new drug

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We have focussed on the mast cells appearing in salivary gland, oral mucosa, and other tissues, and examined the bioactive substances present in these cells. We found that the mast cells present in these tissues and peritoneal cavity expressed high molecular weight-kininogen and T-I kininogen and these protein products were stored in the secretory granules in these cells (2000-2001). On the other hand, the salivary gland cells other than mast cells did not show the kininogen expression, although there are reports indicating that these inflammation proteins are expressed in the salivary gland parenchymal cellsOn the other hand, the salivary gland produces the various cytokins other than these inflammation proteins. We therefore examined how the expression of these cytokines are regulated by the inflammation signals prompted in the oral cavity or in the whole body. We also tried to find out the function of the salivary gland in the defense system in the oral cavity. Using C3H/HeJ and C3H … More /HeN mice (mutant strain defective of Toll-like receptor and its wild type strain), we examined how inflammation cytokines were induced by systemic injection of LPS. In vivo experiments, injection of LPS induced the expression of n-1β strongly and TNF-α and IL-6 weakly (2002)We next showed that IL-lei was localized in the secretory granules of the granular convoluted tubular cells. We also found that the size of salivary gland IL-1β is 17 kDa although the mRNA corresponding to 35 kDa IL-1β precursor was synthesized in the submandibular gland. It is therefore conceivable that 35 kDa IL-1β precursor was hydrolyzed to the 17 kDa secretory form in the salivary gland. Since kallikrein mK1, mK9, mK13, and mK22 are localized in the secretory granules of the submandibular gland, we incubated 35 kDa IL-1β with these kallikreins. The result showed that mK13 is an enzyme which gave 17 kDa IL-1β. We are now investigating the cleavage site in 35 kDa IL-1β by mK13Strict defense system would be required for oral cavity since the oral cavity is a major barrier of harmful foreign antigens or bacteria in the body. The present study implies the existence of "Oral cavity Salivary gland axis" as a defense system, by which inflammation occurred in the oral cavity may be healed by interaction with the salivary gland Less