{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T09:39:10Z","timestamp":1784885950219,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,6,18]],"date-time":"2012-06-18T00:00:00Z","timestamp":1339977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:p>Lipopolysaccharide (LPS) can exacerbate asthma; however, the mechanisms are not fully understood. This study investigated the effect of LPS on antigen\u2010stimulated mast cell degranulation and the underlying mechanisms. We found that LPS enhanced degranulation in RBL\u20102H3 cells and mouse peritoneal mast cells upon Fc\u025bRI activation, in a dose\u2010 and time\u2010dependent manner. Parallel to the alteration of degranulation, LPS increased Fc\u025bRI\u2010activated Ca<jats:sup>2+<\/jats:sup> mobilization, as well as Ca<jats:sup>2+<\/jats:sup> entry through store\u2010operated calcium channels (SOCs) evoked by thapsigargin. Blocking Ca<jats:sup>2+<\/jats:sup> entry through SOCs completely abolished LPS enhancement of mast cell degranulation. Consistent with functional alteration of SOCs, LPS increased mRNA and protein levels of Orai1 and STIM1, two major subunits of SOCs, in a time\u2010dependent manner. In addition, LPS increased the mRNA level of Toll\u2010like receptor 4 (TLR4) in a time\u2010dependent manner. Blocking TLR4 with Cli\u2010095 inhibited LPS, increasing transcription and expression of SOC subunits. Concomitantly, the effect of LPS enhancement of Ca<jats:sup>2+<\/jats:sup> mobilization and mast cell degranulation was largely reduced by Cli\u2010095. Administration of LPS (1 \u03bcg) <jats:italic>in vivo<\/jats:italic> aggravated airway hyperreactivity and inflammatory reactions in allergic asthmatic mice. Histamine levels in serum and bronchoalveolar lavage fluid were increased by LPS treatment. In addition, Ca<jats:sup>2+<\/jats:sup> mobilization was enhanced in peritoneal mast cells isolated from LPS\u2010treated asthmatic mice. Taken together, these results imply that LPS enhances mast cell degranulation, which potentially contributes to LPS exacerbating allergic asthma. Lipopolysaccharide increases Ca<jats:sup>2+<\/jats:sup> entry through SOCs by upregulating transcription and expression of SOC subunits, mainly through interacting with TLR4 in mast cells, resulting in enhancement of mast cell degranulation upon antigen stimulation.<\/jats:p>","DOI":"10.1113\/expphysiol.2012.065854","type":"journal-article","created":{"date-parts":[[2012,5,12]],"date-time":"2012-05-12T04:34:48Z","timestamp":1336797288000},"page":"1315-1327","source":"Crossref","is-referenced-by-count":39,"title":["Lipopolysaccharide enhances Fc\u025bRI\u2010mediated mast cell degranulation by increasing Ca<sup>2+<\/sup> entry through store\u2010operated Ca<sup>2+<\/sup> channels: implications for lipopolysaccharide exacerbating allergic 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