title: Role of ERK1/2 kinase in the expression of iNOS by NDMA in human neutrophils.
abstract: Potential role of ERK1/2 kinase in conjunction with p38 in the regulation of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production, and superoxide anion generation by human neutrophils (PMNs) exposed to N-nitrosodimethylamine (NDMA) was determined. Increased synthesis of NO due to the involvement of iNOS in neutrophils exposed to NDMA was observed. In addition, intensified activation of ERK1/2 and p38 kinases was determined in these cells. Inhibition of kinase regulated by extracellular signals (ERK1/2) pathway, in contrast to p38 pathway, led to an increased production of NO and expression of iNOS in PMNs. Moreover, as a result of inhibition of ERK1/2 pathway, a decreased activation of p38 kinase was observed in neutrophils, while inhibition of p38 kinase did not affect activation of ERK1/2 pathway in these cells. An increased ability to release superoxide anion by the studied PMNs was observed, which decreased after ERK1/2 pathway inhibition. In conclusion, in human neutrophils, ERK1/2 kinase is not directly involved in the regulation of iNOS and NO production induced by NDMA; however, the kinase participates in superoxide anion production in these cells.
authors: Department of Immunology Medical University of Bialystok, Waszyngtona 15A, 15-269 Bialystok, Poland. rwioletta@umb.edu.pl
authors: Wioletta
authors: W
authors: Ratajczak-Wrona
authors: Ewa
authors: E
authors: Jablonska
authors: Marzena
authors: M
authors: Garley
authors: Jakub
authors: J
authors: Jablonski
authors: Piotr
authors: P
authors: Radziwon
mesh_terms: D000293:Adolescent; D000328:Adult; D000838:Anions; D004128:Dimethylnitrosamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D008954:Models, Biological; D009504:Neutrophils / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009573:Nitrites / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D013481:Superoxides / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000838:Anions; D004791:Enzyme Inhibitors; D009573:Nitrites; D013481:Superoxides; D052247:Nitric Oxide Synthase Type II; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D004128:Dimethylnitrosamine; D010100:Oxygen