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.
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.
Chen
C C
CC
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan. ccchen@ha.mc.ntu.edu.tw
Chen
J J
JJ
Chou
C Y
CY
D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics*; D007375:Interleukin-1 / Q000502:physiology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000502:physiology; D009154:Mutation; D009281:Naphthalenes / Q000494:pharmacology; D009636:Norbornanes; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051571:Protein Kinase C-alpha; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases; D000097782:NF-kappaB-Inducing Kinase
D001952:Bridged-Ring Compounds; D004791:Enzyme Inhibitors; D005419:Flavonoids; D051550:I-kappa B Kinase; D007093:Imidazoles; D007211:Indoles; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1; D007527:Isoenzymes; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009281:Naphthalenes; D009636:Norbornanes; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011725:Pyridines; D019311:Staurosporine; D013859:Thiocarbamates; D013871:Thiones; D020032:Tyrphostins; D048051:p38 Mitogen-Activated Protein Kinases; D000097782:NF-kappaB-Inducing Kinase; C046498:tricyclodecane-9-yl-xanthogenate; C496559:CHUK protein, human; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C496628:PRKCA protein, human; C058819:calphostin C; C093642:SB 203580; C060641:tyrphostin A23; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; C064758:Ro 31-8220