title: Involvement of p38 MAPK, JNK, p42/p44 ERK and NF-kappaB in IL-1beta-induced chemokine release in human airway smooth muscle cells.
abstract: Asthma is an inflammatory disease, in which eotaxin, MCP-1 and MCP-3 play a crucial role. These chemokines have been shown to be expressed and produced by IL-1beta-stimulated human airway smooth muscle cells (HASMC) in culture. In the present study we were interested to unravel the IL-1beta-induced signal transduction leading to chemokine production. Using Western blot, we observed an activation of p38 MAPK, JNK kinase and p42/p44 ERK when HASMC were stimulated with IL-1beta. We also observed a significant decrease in the expression and the release of eotaxin, MCP-1 and MCP-3 in the presence of SB203580, an inhibitor of p38 MAPK (71 +/- 6%, P < 0.05, n = 8 and 39 +/- 10% P < 0.01, n = 10 respectively), curcumin, an inhibitor of JNK kinase (83 +/- 4.9% and 88 +/- 3.4% respectively, P < 0.01, n = 4). U0126, an inhibitor of p42/p44 ERK, also produced a significant decrease in chemokine production (46.3 +/- 9%, P < 0.01 n = 10 and 67.8 +/- 12%, P < 0.01, n = 12). Pyrrolydine dithiocarbamate, an inhibitor of NF-kappaB was also able to reduce the eotaxin, MCP-1 and MCP-3 expression and production (50 +/- 13%, P < 0.05, n = 10 and 23 +/- 7%, P < 0.05, n = 12). We conclude that p38 MAPK, JNK kinase, ERK and NF-kappaB are involved in the IL-1beta-induced eotaxin, MCP-1, and MCP-3 expression and release in HASMC.
authors.affiliation: Lung Transplantation Unit, Department of Respiratory Diseases, University Hospital Gasthuisberg, 49 Herestraat, Leuven B-3000, Belgium.
authors.forename: Wim A
authors.initials: WA
authors.lastname: Wuyts
authors.forename: Bart M
authors.initials: BM
authors.lastname: Vanaudenaerde
authors.forename: Lieven J
authors.initials: LJ
authors.lastname: Dupont
authors.forename: Maurits G
authors.initials: MG
authors.lastname: Demedts
authors.forename: Geert M
authors.initials: GM
authors.lastname: Verleden
mesh_terms: D001249:Asthma / Q000201:enzymology / Q000276:immunology*; D015152:Blotting, Northern / Q000379:methods; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000378:metabolism; D054410:Chemokine CCL7; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology; D016207:Cytokines; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting / Q000379:methods; D007375:Interleukin-1 / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D013268:Stimulation, Chemical; D013859:Thiocarbamates / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D002070:Butadienes; C515456:CCL11 protein, human; C515450:CCL7 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007375:Interleukin-1; D018945:Monocyte Chemoattractant Proteins; D016328:NF-kappa B; D009570:Nitriles; D011725:Pyridines; D011759:Pyrrolidines; D013859:Thiocarbamates; C113580:U 0126; C020972:pyrrolidine dithiocarbamic acid; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D003474:Curcumin; C093642:SB 203580