The role of MAP kinases in the induction of iNOS expression in neutrophils exposed to NDMA: the involvement transcription factors

• Published in: Advances in medical sciences Vol. 58; no. 2; pp. 265 - 273
• Main Authors: Ratajczak-Wrona, W, Jablonska, E, Garley, M, Jablonski, J, Radziwon, P, Iwaniuk, A
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Urban & Partner Sp. z o.o 01.12.2013; De Gruyter Open; Elsevier Limited
• Subjects: Adult; AP-1 (c-Jun; AP-1 (c-Jun, c-Fos); c-Fos; Dimethylnitrosamine - pharmacology; Gene Expression Regulation, Enzymologic - drug effects; Humans; inducible nitric oxide synthase (iNOS); JNK Mitogen-Activated Protein Kinases - metabolism; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Middle Aged; Mitogen-Activated Protein Kinase 7 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 7 - metabolism; N-nitrosodimethylamine (NDMA); neutrophils (PMNs); Neutrophils - drug effects; Neutrophils - enzymology; NF-κB (p65); nitric oxide (NO); Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; Transcription Factor AP-1 - metabolism; Transcription Factor RelA - metabolism; Xenobiotics - pharmacology; nitric oxide (NO); neutrophils (PMNs); inducible nitric oxide synthase (iNOS); NF-κB (p65); AP-1 (c-Jun, c-Fos); N-nitrosodimethylamine (NDMA)
• ISSN: 1896-1126; 1898-4002
• DOI: 10.2478/v10039-012-0074-y

The role of MAP kinases in the activation of AP-1 (c-Jun, c-Fos) and NF-κB p65 engaged in the regulation of iNOS expression in human neutrophils (PMNs) exposed to N-nitrosodimethylamine (NDMA) was analyzed in the study. The study included a group of 20 healthy individuals. Isolated human PMN were incubated in the presence of NDMA. Selective MAP kinases inhibitors were used. The expression of proteins in the cytoplasmic and nuclear fractions was assessed using Western blot method. The results show that NDMA intensifies iNOS, c-Jun, NF-κB p65 and IκB-α expression in the analyzed PMNs. The blocking of the p38 pathway led to lower iNOS expression, and higher expression of c-Jun and c-Fos in the cytoplasmic fraction, and also lower c-Jun expression in the nuclear fraction of PMNs exposed to NDMA. A decrease in iNOS expression in the cytoplasmic fraction, and also c-Jun in both fractions of the examined cells, was observed as a result of JNK pathway inhibition. The blocking of the ERK5 pathway led to higher iNOS, c-Jun and c-Fos expression in the cytoplasmic fraction, and higher c-Jun expression in the nuclear fraction of PMNs exposed to NDMA. The study also demonstrated that blocking of the p38 and JNK pathways resulted in higher expression of NF-κB p65 and IκB-α in the cytoplasmic fraction and their lower expression in the nuclear fraction of these cells. Our data indicate the role of MAP kinases p38 and JNK in the activation of c-Jun and NF-κB p65 transcription factors engaged in the regulation of iNOS expression in human neutrophils exposed to NDMA. However ERK5 kinase is not involved in the regulation of iNOS and NO production by those cells.