The signaling pathway of protein kinase C (PKC) is known to play a role in mediating the action of various cytokines. Here we examined the signal transduction pathway of PKC activation and the role of PKC isoforms in interleukin-1β (IL-1β)-mediated cyclooxygenase-2 (COX-2) expression in human pulmonary epithelial cell line (A549). The tyrosine kinase inhibitors (genistein and tyrphostin AG126) and phosphatidylcholine-phospholipase C inhibitor (D-609) prevented IL-1β-induced prostaglandin E2 (PGE2) release and COX-2 expression, whereas U-73122 (a phosphatidylinositol-phospholipase C inhibitor) and propranolol (a phosphatidate phosphohydrolase inhibitor) had no effect. The PKC inhibitors (Go 6976 and Ro 31-8220) and NF-κB inhibitor, pyrrolidine dithiocarbamate, also attenuated IL-1β-induced PGE2 release and COX-2 expression. Western blot analysis using PKC isoenzyme-specific antibodies indicated that A549 cells expressed PKC-α, -γ, ι, -λ, -ζ and -μ. IL-1β caused the translocation of PKC-γ, but not other isoforms from cytosol to the membrane fraction. Moreover, the translocation of PKC-γ, was inhibited by genistein or D-609, but not by U-73122. IL-1β caused the translocation of p65 NF-κB from cytosol to the nucleus as well as the degradation of IκB-α in cytosol. Furthermore, the translocation of p65 NF- κB was inhibited by genistein, Go 6976, Ro 31-8220, or pyrrolidine dithiocarbamate. These results indicate that in human pulmonary, epithelial cells, IL-1β might activate phosphatidylcholine-phospholipase C through an upstream tyrosine phosphorylation to elicit PKC activation, which in turn initiates NF-κB activation and finally induces COX-2 expression and PGE2 release. Of the PKC isoforms present in A549 cells, only activation of PKC- γ, is involved in regulating IL-1β induced responses.

Original languageEnglish
Pages (from-to)36-43
Number of pages8
JournalMolecular Pharmacology
Issue number1
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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