Protein kinase Cα but not p44/42 mitogen-activated protein kinase, p38, or c-Jun NH2-terminal kinase is required for intercellular adhesion molecule-1 expression mediated by interleukin-1β:: Involvement of sequential activation of tyrosine kinase, nuclear factor-κB-inducing kinase, and IκB kinase 2

IL-1 beta 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-1 beta -induced ICAM-1 expression. IL-1 beta 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-1 beta -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-1 beta 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-1 beta -induced ICAM-1 expression. NF-kappaB DNA-protein binding and ICAM-1 promoter activity were enhanced by IL-1 beta 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 PKC alpha, NIK, or IKK2, but not IKK1 mutant, inhibited IL-1 beta- or TPA-induced ICAM-1 promoter activity. IKK activity was stimulated by either IL-1 beta or TPA, and these effects were inhibited by Ro 31-8220 or tyrphostin 23. Taken together, IL-1 beta activates phosphatidylcholine-specific phospholipase C and induces activation of PKC alpha 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.