Protein kinase calpha but not p44/42 mitogen-activated protein kinase, p38, or c-Jun NH(2)-terminal kinase is required for intercellular adhesion molecule-1 expression mediated by interleukin-1beta: involvement of sequential activation of tyrosine kinase, nuclear factor-kappaB-inducing kinase, and IkappaB kinase 2

Mol Pharmacol. 2000 Dec;58(6):1479-89. doi: 10.1124/mol.58.6.1479.

Abstract

IL-1beta induced an increase in ICAM-1 expression in human A549 epithelial cells and immunofluorescence staining confirmed this result. Tyrosine kinase inhibitors (genistein or tyrphostin 23) or phosphatidylcholine-specific phospholipase C inhibitor (D609) attenuated IL-1beta-induced ICAM-1 expression. IL-1beta produced an increase in PKC activity and this effect was abolished by D609. PKC inhibitors (staurosporine, Ro 31-8220, calphostin C, or Go 6976) also inhibited IL-1beta-induced response. TPA, a PKC activator, stimulated ICAM-1 expression as well, this effect being inhibited by tyrosine kinase inhibitors. Treatment of cells with IL-1beta resulted in stimulation of p44/42 MAPK, p38, and JNK. However, neither the mitogen activated protein kinase kinase inhibitor PD 98059 nor the p38 inhibitor SB 203580 affected IL-1beta-induced ICAM-1 expression. NF-kappaB DNA-protein binding and ICAM-1 promoter activity were enhanced by IL-1beta and these effects were inhibited by tyrphostin 23, but not by PD 98059 or SB 203580. TPA also stimulated NF-kappaB DNA-protein binding and ICAM-1 promoter activity as well, these effects being inhibited by tyrosine kinase inhibitors. Dominant-negative PKCalpha, NIK, or IKK2, but not IKK1 mutant, inhibited IL-1beta- or TPA-induced ICAM-1 promoter activity. IKK activity was stimulated by either IL-1beta or TPA, and these effects were inhibited by Ro 31-8220 or tyrphostin 23. Taken together, IL-1beta activates phosphatidylcholine-specific phospholipase C and induces activation of PKCalpha and protein tyrosine kinase, resulting in the stimulation of NIK, IKK2, and NF-kappaB in the ICAM-1 promoter, then initiation of ICAM-1 expression. However, activation of p44/42 MAPK, p38, and JNK is not involved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bridged-Ring Compounds / pharmacology
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Fluorescent Antibody Technique
  • Gene Expression / drug effects
  • Gene Expression / physiology*
  • Humans
  • I-kappa B Kinase
  • Imidazoles / pharmacology
  • Indoles / pharmacology
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Intercellular Adhesion Molecule-1 / genetics*
  • Interleukin-1 / physiology*
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / physiology*
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / physiology
  • Mutation
  • Naphthalenes / pharmacology
  • Norbornanes
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / physiology*
  • Protein Kinase C-alpha
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / physiology
  • Pyridines / pharmacology
  • Staurosporine / pharmacology
  • Thiocarbamates
  • Thiones / pharmacology
  • Tyrphostins / pharmacology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Bridged-Ring Compounds
  • Enzyme Inhibitors
  • Flavonoids
  • Imidazoles
  • Indoles
  • Interleukin-1
  • Isoenzymes
  • Naphthalenes
  • Norbornanes
  • Pyridines
  • Thiocarbamates
  • Thiones
  • Tyrphostins
  • Intercellular Adhesion Molecule-1
  • tricyclodecane-9-yl-xanthogenate
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • PRKCA protein, human
  • Protein Kinase C
  • Protein Kinase C-alpha
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • NF-kappa B kinase
  • Staurosporine
  • calphostin C
  • SB 203580
  • tyrphostin A23
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Ro 31-8220