摘要
Background Cigarette smoke induced airway inflammation plays a role in pathogenesis of airway inflammation.Resolvin-D1 derived from omega-3 polyunsaturated fatty acids is an endogenous anti-inflammatory and proresolving lipid mediator.Resolvin-D1 ameliorated inflammatory responses in lung injury,asthma,peritonitis and atherosclerosis.We investigated whether resolvin-D1 suppressed the productions of chemokines and oxidative stress induced by cigarette smoke extract （CSE） in vitro and its possible mechanism.Methods We examined the proinfiammatory chemokine interleukin-8 and hydrogen peroxide （H2O2）productions induced by CSE in 16 human bronchial epithelial （16HBE）cells after resolvin-D1 treatment and their mechanisms.16HBE cells were treated with resolvin-D1 at up to 10 nmol/L,for 30 minutes before CSE up to 16％ （v/v） exposure.Release of interlukin-8 proteins was assessed by enzyme linked immunosort assay （ELISA） and its mRNA level by RT-PCR.We evaluated extracellular H2O2 expression in the supematant.Phosphorylation of NF-KB/p65 and degradation of Ⅰ-KB in 16HBE cells were determined by Westem blotting analysis and NF-KB DNA binding activity by electrophoretic mobility shift assay （EMSA）.Results 16HBE cells treated with 8％ CSE showed significantly higher interlukin-8 production.Resolvin-D1 pretreatment inhibited CSE induced intedukin-8 production （mRNA and protein） in a dose and time dependent manner.Extracellular H2O2 level decreased after resolvin-D1 treatment.Resolvin-D1 attenuated CSE triggered Ⅰ-KB degradation and NF-KB/p65 activation dose dependently and inhibited NF-KB DNA binding activity.Conclusion Resolvin-D1 inhibits CSE induced interlukin-8 and H2O2 production in 16HBE cells by modulating NF-KB activation and has therapeutic potential for pulmonary inflammation.
Background Cigarette smoke induced airway inflammation plays a role in pathogenesis of airway inflammation.Resolvin-D1 derived from omega-3 polyunsaturated fatty acids is an endogenous anti-inflammatory and proresolving lipid mediator.Resolvin-D1 ameliorated inflammatory responses in lung injury,asthma,peritonitis and atherosclerosis.We investigated whether resolvin-D1 suppressed the productions of chemokines and oxidative stress induced by cigarette smoke extract （CSE） in vitro and its possible mechanism.Methods We examined the proinfiammatory chemokine interleukin-8 and hydrogen peroxide （H2O2）productions induced by CSE in 16 human bronchial epithelial （16HBE）cells after resolvin-D1 treatment and their mechanisms.16HBE cells were treated with resolvin-D1 at up to 10 nmol/L,for 30 minutes before CSE up to 16％ （v/v） exposure.Release of interlukin-8 proteins was assessed by enzyme linked immunosort assay （ELISA） and its mRNA level by RT-PCR.We evaluated extracellular H2O2 expression in the supematant.Phosphorylation of NF-KB/p65 and degradation of Ⅰ-KB in 16HBE cells were determined by Westem blotting analysis and NF-KB DNA binding activity by electrophoretic mobility shift assay （EMSA）.Results 16HBE cells treated with 8％ CSE showed significantly higher interlukin-8 production.Resolvin-D1 pretreatment inhibited CSE induced intedukin-8 production （mRNA and protein） in a dose and time dependent manner.Extracellular H2O2 level decreased after resolvin-D1 treatment.Resolvin-D1 attenuated CSE triggered Ⅰ-KB degradation and NF-KB/p65 activation dose dependently and inhibited NF-KB DNA binding activity.Conclusion Resolvin-D1 inhibits CSE induced interlukin-8 and H2O2 production in 16HBE cells by modulating NF-KB activation and has therapeutic potential for pulmonary inflammation.
基金
This study was supported by grants from the National Natural Science Foundation of China and China Medical Board of New York to Dr.Wen Fuqiang （No.31171103,No.81230001 and No.06834）.
