Involvement of p38 MAPK, JNK, p42/p44 ERK and NF-kappaB in IL-1beta-induced chemokine release in human airway smooth muscle cells

Respir Med. 2003 Jul;97(7):811-7. doi: 10.1016/s0954-6111(03)00036-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / enzymology
  • Asthma / immunology*
  • Blotting, Northern / methods
  • Butadienes / pharmacology
  • Cells, Cultured
  • Chemokine CCL11
  • Chemokine CCL2 / metabolism
  • Chemokine CCL7
  • Chemokines / metabolism*
  • Chemokines, CC / metabolism
  • Curcumin / pharmacology
  • Cytokines*
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Imidazoles / pharmacology
  • Immunoblotting / methods
  • Interleukin-1 / pharmacology*
  • JNK Mitogen-Activated Protein Kinases*
  • MAP Kinase Kinase 4
  • MAP Kinase Signaling System*
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Monocyte Chemoattractant Proteins / metabolism
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / enzymology
  • Muscle, Smooth / immunology
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Nitriles / pharmacology
  • Phosphorylation
  • Pyridines / pharmacology
  • Pyrrolidines / pharmacology
  • Stimulation, Chemical
  • Thiocarbamates / pharmacology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Butadienes
  • CCL11 protein, human
  • CCL7 protein, human
  • Chemokine CCL11
  • Chemokine CCL2
  • Chemokine CCL7
  • Chemokines
  • Chemokines, CC
  • Cytokines
  • Enzyme Inhibitors
  • Imidazoles
  • Interleukin-1
  • Monocyte Chemoattractant Proteins
  • NF-kappa B
  • Nitriles
  • Pyridines
  • Pyrrolidines
  • Thiocarbamates
  • U 0126
  • pyrrolidine dithiocarbamic acid
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • Curcumin
  • SB 203580