title: N-acetylcysteine reduces chemokine release via inhibition of p38 MAPK in human airway smooth muscle cells.
abstract: Reactive oxygen species are involved in the activation of several mitogen-activated protein kinases (MAPKs), key-players in the production of several cytokines. Therefore the current study investigated whether N-acetylcysteine (NAC), an antioxidative agent, inhibits the interleukin (IL)-1beta-induced expression and production of eotaxin and monocyte chemotactic protein (MCP)-1 in human airway smooth muscle cells (HASMC). NAC (10 mM) decreased the expression of eotaxin and MCP-1, by 46 +/- 11% (n=7) and 87 +/- 4% (n=6), respectively; the eotaxin release was inhibited by 75 +/- 5% (n=7), whereas the MCP-1 release was decreased by 69 +/- 41% (n=10). NAC (1 mM) also decreased the IL-1beta-induced activation of p38 MAPK. Compared with unstimulated cells, a four-fold increase in 8-isoprostane production in IL-1beta-stimulated HASMC was observed, which could be inhibited by NAC in a concentration-dependent way, with a maximum inhibition of 39 +/- 12%, with 1 mM NAC. The present study demonstrated that N-acetylcysteine inhibits the interleukin-1beta-induced eotaxin and monocyte chemotactic protein 1 expression and production due to a decreased activation of p38 mitogen-activated protein kinase. This study has also shown that N-acetylcysteine decreases the interleukin-1beta-induced production of reactive oxygen species, as suggested by a reduction in the 8-isoprostane production.
authors.affiliation: KU Leuven, Laboratory of Pneumology, Leuven, Belgium.
authors.forename: W A
authors.initials: WA
authors.lastname: Wuyts
authors.forename: B M
authors.initials: BM
authors.lastname: Vanaudenaerde
authors.forename: L J
authors.initials: LJ
authors.lastname: Dupont
authors.forename: M G
authors.initials: MG
authors.lastname: Demedts
authors.forename: G M
authors.initials: GM
authors.lastname: Verleden
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D001249:Asthma / Q000201:enzymology / Q000276:immunology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives*; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D028441:F2-Isoprostanes / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D015398:Signal Transduction; D018709:Statistics, Nonparametric; D013268:Stimulation, Chemical; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D018925:Chemokines; D019742:Chemokines, CC; D028441:F2-Isoprostanes; D007375:Interleukin-1; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D000111:Acetylcysteine