Lipopolysaccharide enhances FcɛRI‐mediated mast cell degranulation by increasing Ca2+ entry through store‐operated Ca2+ channels: implications for lipopolysaccharide exacerbating allergic asthma

摘要: Lipopolysaccharide (LPS) can exacerbate asthma; however, the mechanisms are not fully understood. This study investigated effect of LPS on antigen-stimulated mast cell degranulation and underlying mechanisms. We found that enhanced in RBL-2H3 cells mouse peritoneal upon FceRI activation, a dose- time-dependent manner. Parallel to alteration degranulation, increased FceRI-activated Ca(2+) mobilization, as well entry through store-operated calcium channels (SOCs) evoked by thapsigargin. Blocking SOCs completely abolished enhancement degranulation. Consistent with functional SOCs, mRNA protein levels Orai1 STIM1, two major subunits In addition, level Toll-like receptor 4 (TLR4) TLR4 Cli-095 inhibited LPS, increasing transcription expression SOC subunits. Concomitantly, mobilization was largely reduced Cli-095. Administration (1 μg) vivo aggravated airway hyperreactivity inflammatory reactions allergic asthmatic mice. Histamine serum bronchoalveolar lavage fluid were treatment. isolated from LPS-treated Taken together, these results imply enhances which potentially contributes exacerbating asthma. increases upregulating subunits, mainly interacting cells, resulting antigen stimulation.