title: Activation of TRPV1-dependent calcium oscillation exacerbates seawater inhalation-induced acute lung injury.
abstract: Calcium is an important second messenger and it is widely recognized that acute lung injury (ALI) is often caused by oscillations of cytosolic free Ca2+. Previous studies have indicated that the activation of transient receptor potential‑vanilloid (TRPV) channels and subsequent Ca2+ entry initiates an acute calcium‑dependent permeability increase during ALI. However, whether seawater exposure induces such an effect through the activation of TRPV channels remains unknown. In the current study, the effect of calcium, a component of seawater, on the inflammatory reactions that occur during seawater drowning‑induced ALI, was examined. The results demonstrated that a high concentration of calcium ions in seawater increased lung tissue myeloperoxidase activity and the secretion of inflammatory mediators, such as tumor necrosis factor‑α (TNF‑α) and interleukin (IL)‑1β and IL‑6. Further study demonstrated that the seawater challenge elevated cytosolic Ca2+ concentration, indicated by [Ca2+]c, by inducing calcium influx from the extracellular medium via TRPV1 channels. The elevated [Ca2+c] may have resulted in the increased release of TNF‑α and IL‑1β via increased phosphorylation of nuclear factor‑κB (NF‑κB). It was concluded that a high concentration of calcium in seawater exacerbated lung injury, and TRPV1 channels were notable mediators of the calcium increase initiated by the seawater challenge. Calcium influx through TRPV1 may have led to greater phosphorylation of NF‑κB and increased release of TNF‑α and IL‑1β.
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Bo
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Dunquan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Faguang
authors.initials: F
authors.lastname: Jin
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D055371:Acute Lung Injury; D000280:Administration, Inhalation; D000818:Animals; D002118:Calcium / Q000378:metabolism; D065096:Calcium Chelating Agents / Q000494:pharmacology; D020013:Calcium Signaling; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D018450:Disease Progression; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012623:Seawater; D050916:TRPV Cation Channels / Q000378:metabolism*; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D065096:Calcium Chelating Agents; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016328:NF-kappa B; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D013859:Thiocarbamates; C493922:Trpv1 protein, rat; D014409:Tumor Necrosis Factor-alpha; C066229:prolinedithiocarbamate; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D011392:Proline; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium