title: The presence of serotonin in cigarette smoke - a possible mechanistic link to 5-HT-induced airway inflammation.
abstract: We previously reported the involvement of serotonin (5-HT) metabolism in cigarette smoke-induced oxidative stress in rat lung in vivo. Here, we report cigarette smoke as a source of serotonin (5-HT) to the airways and aim at investigating the effects of 5-HT on oxidative stress and inflammation in human bronchial epithelial cells (BEAS-2B). A 5-HT analog was identified to be present in aqueous phase cigarette smoke using the LC-MS/MS approach, which was later confirmed by a 5-HT enzyme-linked immune assay (EIA). Furthermore, exposure to 5-HT caused a time-dependent elevation of intracellular ROS level, which was blocked in the presence of apocynin (a NOX inhibitor). In support, the immunoblot analysis indicated that there was an increase in the expression of NOX2 time-dependently. 5-HT-induced elevation of IL-8 at both mRNA and protein levels was observed, which was inhibited by TEMPOL (a free radical scavenger), and inhibitors for p38 MAPK (SB203580) and ERK (U0126), in line with the time-dependent phosphorylation of p38 MAPK and ERK. In conclusion, our findings suggest that 5-HT presented in bronchial epithelium of smokers may be involved in cigarette smoke-induced oxidative stress and inflammation via activation of p38 MAPK and ERK pathway after the formation of free radicals.
authors.affiliation: a Department of Medicine , The University of Hong Kong , Hong Kong SAR, China ;
authors.forename: Way Kwok Wai
authors.initials: WK
authors.lastname: Lau
authors.affiliation: a Department of Medicine , The University of Hong Kong , Hong Kong SAR, China ;
authors.forename: Louise Yuting
authors.initials: LY
authors.lastname: Cui
authors.affiliation: a Department of Medicine , The University of Hong Kong , Hong Kong SAR, China ;|b Department of Biochemistry , The University of Hong Kong , Hong Kong SAR, China ;
authors.forename: Stanley Chi Hang
authors.initials: SC
authors.lastname: Chan
authors.affiliation: a Department of Medicine , The University of Hong Kong , Hong Kong SAR, China ;|d Department of Pharmacology and Pharmacy , The University of Hong Kong , Hong Kong SAR, China.
authors.forename: Mary Sau Man
authors.initials: MS
authors.lastname: Ip
authors.affiliation: a Department of Medicine , The University of Hong Kong , Hong Kong SAR, China ;|c Research Centre of Heart, Brain, Hormone and Healthy Aging , The University of Hong Kong , Hong Kong SAR, China ;|d Department of Pharmacology and Pharmacy , The University of Hong Kong , Hong Kong SAR, China.
authors.forename: Judith Choi Wo
authors.initials: JC
authors.lastname: Mak
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D002070:Butadienes / Q000008:administration & dosage; D003497:Cyclic N-Oxides / Q000008:administration & dosage; D005609:Free Radicals / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009570:Nitriles / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects*; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012701:Serotonin / Q000302:isolation & purification / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects; D013113:Spin Labels; D053719:Tandem Mass Spectrometry; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002070:Butadienes; D003497:Cyclic N-Oxides; D005609:Free Radicals; D007093:Imidazoles; D009570:Nitriles; D011725:Pyridines; D017382:Reactive Oxygen Species; D013113:Spin Labels; C113580:U 0126; D012701:Serotonin; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C001803:tempol
keywords: Airway inflammation; cigarette smoking; interleukin-8; reactive oxygen species; serotonin