Expression of mitogen-inducible cyclooxygenase induced by lipopolysaccharide: Mediation through both mitogen-activated protein kinase and nf-kb signaling pathways in macrophages

doi:10.1016/S0006-2952(97)00154-8

Biochemical Pharmacology

Volume 54, Issue 1, 1 July 1997, Pages 87-96

https://doi.org/10.1016/S0006-2952(97)00154-8 Get rights and content

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-ϰB 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-κB 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-ϰB 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 IκB-α. Together, these results indicate that the activation of NF-ϰB 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.

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^☆: This work was supported, in part, by National Institutes of Health Grant R01 DK-41868 and United States Department of Agriculture Grant 93-37200-8961.

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Research paperExpression of mitogen-inducible cyclooxygenase induced by lipopolysaccharide: Mediation through both mitogen-activated protein kinase and nf-kb signaling pathways in macrophages☆

Abstract

J Biol Chem

FEBS Lett

J Biol Chem

Biochem Biophys Res Commun

J Biol Chem

J Biol Chem

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Arch Biochem Biophys

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J Biol Chem

J Biol Chem

Trends Biochem Sci

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Cell

Cell

J Biol Chem

Curr Biol

J Bio! Chem

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

Biochim Biophys Acta

Anal Biochem

Research paper
Expression of mitogen-inducible cyclooxygenase induced by lipopolysaccharide: Mediation through both mitogen-activated protein kinase and nf-kb signaling pathways in macrophages☆