title: Different mechanism of LPS-induced calcium increase in human lung epithelial cell and microvascular endothelial cell: a cell culture study in a model for ARDS.
abstract: Acute respiratory distress syndrome (ARDS) is a contemporary term incorporating the historic 'acute lung injury' and the colloquial term 'shock lung'. ARDS remains a serious and enigmatic human disease, causing significant mortality. The mechanisms involved at the alveolar cell/capillary endothelial interface have been explored but to date we lack clarity on the role of intracellular calcium ([Ca(2+)]i) fluxes across this interface. To explore the mechanisms of Ca(2+) induced inflammatory reaction in epithelial cells and pulmonary microvascular endothelial cells (HMVEC) located at the two sides of blood-air barrier, lung epithelial A549 and HMVEC cells were treated with LPS. Our results demonstrated that LPS evoked the increase of [Ca(2+)]i, TNF-α and IL-8 in both cells types. The [Ca(2+)]i increases involved intracellular but not extracellular Ca(2+) sources in A549, but both intracellular and extracellular Ca(2+) sources in HMVEC cells. The effects of LPS on both cells types were completely inhibited by the combination of LPS and CaSR-targeted siRNA. Furthermore, LPS-inhibited cell proliferations were significantly reversed by the combined treatment. Therefore, LPS induced different mechanisms of [Ca(2+)]i increase during the activation of CaSR in A549 and HMVEC cells, which translates into functional outputs related to ARDS.
authors.affiliation: Ningbo Medical Center, LiHuiLi Hospital, Medical School, Ningbo University, Ningbo, 315041, China.
authors.forename: Kejing
authors.initials: K
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Shuaishuai
authors.initials: S
authors.lastname: Huang
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Taohong
authors.initials: T
authors.lastname: Li
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Jin
authors.forename: Michael
authors.initials: M
authors.lastname: Hehir
authors.forename: Chiyi
authors.initials: C
authors.lastname: Xu
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D044169:Receptors, Calcium-Sensing; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium