Activation of the JAK/STAT pathway in human neutrophils by NDMA

Authors: WIOLETTA RATAJCZAK WRONA, EWA JABLONSKA, MARZENA GARLEY, JAKUB JABLONSKI, PIOTR RADZIWON, AGNIESZKA IWANIUK

Abstract: The study objective was to assess the role of the JAK/STAT pathway in the induction of nitric oxide (NO) synthesis with the involvement of inducible nitric oxide synthase (iNOS) and in the generation of superoxide anion radical by human neutrophils (PMNs) exposed to N-nitrosodimethylamine (NDMA). Isolated PMNs were incubated in the presence of NDMA. The expression of the study proteins in the cytoplasmic and nuclear fraction was determined by western blotting. Total NO was assayed in cell cultures by Griess reaction. The ability of PMNs to generate superoxide anion radical was assessed using the cytochrome-c reduction test. The current results indicate that NDMA potentiates the expression of iNOS and phospho-JAK2 in the cytoplasmic fraction of human PMNs. Moreover, it increases the expression of phospho-STAT1 and phospho-STAT3 in both fractions of the cells studied. PMNs treated with NDMA showed greater capability to release NO and superoxide anion radical, which was reduced after administration of the JAK/STAT pathway inhibitor. The current findings indicate that NDMA in PMNs activates the JAK/STAT pathway, which plays a role in the production of NO with the involvement of iNOS and in the generation of superoxide anion radical by these cells.

Keywords: Neutrophils, N-nitrosodimethylamine, inducible nitric oxide synthase, nitric oxide, superoxide anion radical, JAK/STAT

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