title: Vitamin C forestalls cigarette smoke induced NF-κB activation in alveolar epithelial cells.
abstract: Cigarette smoking causes cellular oxidative stress resulting in inflammatory diseases of lung wherein transcription factor NF-κB plays an important role. It is possible that vitamin C, an antioxidant, may prevent cigarette smoke (CS)-induced NF-κB activation that involves degradation of I-κBε and nuclear translocation of c-Rel/p50 in alveolar epithelial cells. Therefore, to examine the hypothesis, we verified the effect of vitamin C on CS-induced expression of NF-κB driven luciferase reporter and NF-κB binding at its target DNA by EMSA in alveolar epithelial A549 cells. We also examined the level of I-κBε and sub-cellular distribution of c-Rel by western blotting and immunofluorescence respectively in CSE-treated A549 cells with or without vitamin C pretreatment. We observed a significant reduction in CSE induced luciferase expression, NF-κB DNA binding, I-κBε degradation and c-Rel nuclear translocation in cells pretreated with vitamin C. To further validate the result, we examined sub-cellular distribution of c-Rel in lungs of CS-exposed guinea pigs treated or untreated with vitamin C. Result showed that vitamin C treatment resulted in markedly reduced c-Rel nuclear translocation. All these results demonstrate that vitamin C prevents CS(E)-induced NF-κB activation and thus it could be used for the prevention of CS-induced inflammatory diseases.
authors.affiliation: Department of Microbiology, University of Calcutta, 35 B. C. Road, Kolkata 700019, India.
authors.forename: Bannhi
authors.initials: B
authors.lastname: Das
authors.forename: Palash C
authors.initials: PC
authors.lastname: Maity
authors.forename: Alok K
authors.initials: AK
authors.lastname: Sil
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002460:Cell Line; D004336:Drug Antagonism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
chemical_list: D000975:Antioxidants; D020672:I-kappa B Proteins; C105627:NFKBIE protein, human; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D012906:Smoke; D001205:Ascorbic Acid