These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Expression of mitogen-inducible cyclooxygenase induced by lipopolysaccharide: mediation through both mitogen-activated protein kinase and NF-kappaB signaling pathways in macrophages.
    Author: Hwang D, Jang BC, Yu G, Boudreau M.
    Journal: Biochem Pharmacol; 1997 Jul 01; 54(1):87-96. PubMed ID: 9296354.
    Abstract:
    The mitogen-inducible cyclooxygenase (COX-2) is selectively expressed in lipopolysaccharide (LPS)-stimulated macrophages. However, the signaling pathways that lead to the expression of COX-2 in LPS-stimulated macrophages are not well understood. LPS activates members of mitogen-activated protein kinases (MAPKs) and NF-kappaB transcription factor in macrophages. We have shown that protein tyrosine kinase (PTK) inhibitors suppress the LPS-induced expression of COX-2 in macrophages (Chanmugam et al., J Biol Chem 270: 5418-5426, 1995). These PTK inhibitors also inhibit LPS-induced activation of MAPKs. Thus, in the present study, we determined whether the activation of MAPKs and NF-kappaB is necessary for the signaling pathway for the LPS-induced expression of COX-2 in the murine macrophage cell line RAW 264.7. The findings demonstrated that inhibition of extracellular signal-regulated protein kinases 1 and 2 (ERK-1 and -2) by the selective inhibitor PD98059 or inhibition of P38 by the specific inhibitor SB203580 results in partial suppression of COX-2 expression. However, activation of MAPKs by phorbol 12-myristate 13-acetate, H2O2, sorbitol, sodium vanadate, or a combination of these agents failed to induce the expression of COX-2. Inhibitors of NF-kappaB suppressed COX-2 expression without affecting tyrosine phosphorylation of MAPKs. The PTK inhibitors that suppressed the activation of MAPKs and COX-2 expression also inhibited the degradation of IkappaB-alpha. Together, these results indicate that the activation of NF-kappaB is required to induce the expression of COX-2 in LPS-stimulated RAW 264.7 cells. Inhibition of ERK-1 and 2 or P38 results in partial suppression of COX-2 expression. However, the activation of MAPKs alone is not sufficient to induce the expression of COX-2 in these cells.
    [Abstract] [Full Text] [Related] [New Search]