Passive sensitization increases histamine-stimulated calcium signaling and NF-κB transcription activ

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:lzbenz
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Aim:To find out if the two aspects of asthma(chronic airway inflammation andbronchial hyperresponsiveness)are related to hypersensitivity of calcium signal-ing in bronchial epithelial cells.Methods:Porcine bronchial epithelial cells(PBEC)were divided into sensitized(S)and nonsesitized(N)groups.In group S,the cellswere preincubated with serum from ovalbumin sensitized guinea pigs.In group N,the cells were preincubated with serum from nonsensitized guinea pigs.Singlecell calcium imaging and ELISA-based NF-κ3 activity were used to evaluate thehistamine-stimulated intracellular free calcium level and NF-κB activity,respectively.Results:First,0.1μmol/L histamine could induce [Ca~(2+)]_i oscillationsin PBEC of group S,but not in group N.Second,1/Jmol/L histamine could induce[Ca~(2+)]_i oscillations of PBEC in both group S and group N.The [Ca~(2+)]_i oscillationfrequency of PBEC was significantly higher in group S than in group N,thoughthe[Ca~(2+)]_i oscillation amplitude showed no difference between the two groups.Finally,when 10 μmol/L histamine was used to stimulate PBEC a transient initialincrease followed by a sustained elevation(FSE)of [Ca~(2+)]_i was observed in PBECin both groups.The amplitude of the FSE of [Ca~(2+)]_i in PBEC was significantlyhigher in group S than in group N.The subsequent NF-κB activity was in accor-dance to the calcium oscillation frequency evoked by histamine,but not to theamplitude.Conclusion:It was suggested that the increased sensitivity of calciumsignaling in bronchial epithelial cells might contribute to the exorbitant inflamma-tion or increased susceptibility in asthmatic airway epithelial cells. Aim: To find out if the two aspects of asthma (chronic airway inflammation andbronchial hyperresponsiveness) are related to hypersensitivity of calcium signal-ing in bronchial epithelial cells. Methods: Porcine bronchial epithelial cells (PBEC) were divided into sensitized (S) and nonsesitized (N) groups.In group S, the cells were preincubated with serum from ovalbumin sensitized guinea pigs.In group N, the cells were preincubated with serum from nonsensitized guinea pigs.Singlecell calcium imaging and ELISA-based NF-κΙ activity were used to evaluate thehistamine-stimulated intracellular free calcium level and NF-κB activity, respectively. Results: First, 0.1 μmol / L histamine could induce [Ca 2+] _ I oscillationsin PBEC of group S, but not in group N.Second, 1 / Jmol / L histamine could induce [Ca ~ (2 +)] _i oscillations of PBEC in both groups S and group N. The [Ca ~ (2 +)] _i oscillation frequency of PBEC was significantly higher in group S than in group N , thoughthe [Ca ~ (2 +)] _i oscillation amplitude showed no differe nce between the two groups. Finaally, when 10 μmol / L histamine was used to stimulate PBEC a transient initial increase following a sustained elevation (FSE) of [Ca ~ (2 +)] _ i was observed in PBECin both groups. The amplitude of the FSE of [Ca ~ (2 +)] _i in PBEC was significantlyhigher in group S than in group N. The subsequent NF-κB activity was in accor-dance to the calcium oscillation frequency evoked by histamine, but not to the amplitude. Conlusion : It was suggested that the increased sensitivity of calcium signaling in bronchial epithelial cells might contribute to the exorbitant inflamma- tion or increased susceptibility in asthmatic airway epithelial cells.
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