Tags

Type your tag names separated by a space and hit enter

p38 mitogen-activated protein kinase down-regulates nitric oxide and up-regulates prostaglandin E2 biosynthesis stimulated by interleukin-1beta.
J Biol Chem. 1997 Mar 21; 272(12):8083-9.JB

Abstract

The inflammatory cytokine interleukin 1beta (IL-1beta) induces both cyclooxygenase-2 (Cox-2) and the inducible nitric-oxide synthase (iNOS) with increases in the release of prostaglandins (PGs) and nitric oxide (NO) from glomerular mesangial cells. However, the intracellular signaling mechanisms by which IL-1beta induces iNOS and Cox-2 expression is obscure. Our current studies demonstrate that IL-1beta produces a rapid increase in p38 mitogen-activated protein kinase (MAPK) phosphorylation and activation. Serum starvation and SC68376, a drug which selectively inhibits p38 MAPK in mesangial cells, were used to investigate whether p38 MAPK contributes to the signaling mechanism of IL-1beta induction of NO and PG synthesis. Serum starvation and SC68376 selectively inhibited IL-1beta-induced activation of p38 MAPK. Both SC68376 and serum starvation enhanced NO biosynthesis by increasing iNOS mRNA expression, protein expression, and nitrite production. In contrast, both SC68376 and serum starvation suppressed PG release by inhibiting Cox-2 mRNA, protein expression, and PGE2 synthesis. These data demonstrate that IL-1beta phosphorylates and activates p38 MAPK in mesangial cells. The activation of p38 MAPK may provide a crucial signaling mechanism, which mediates the up-regulation of PG synthesis and the down-regulation of NO biosynthesis induced by IL-1beta.

Authors+Show Affiliations

Department of Molecular Biology & Pharmacology and Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9065483

Citation

Guan, Z, et al. "P38 Mitogen-activated Protein Kinase Down-regulates Nitric Oxide and Up-regulates Prostaglandin E2 Biosynthesis Stimulated By Interleukin-1beta." The Journal of Biological Chemistry, vol. 272, no. 12, 1997, pp. 8083-9.
Guan Z, Baier LD, Morrison AR. P38 mitogen-activated protein kinase down-regulates nitric oxide and up-regulates prostaglandin E2 biosynthesis stimulated by interleukin-1beta. J Biol Chem. 1997;272(12):8083-9.
Guan, Z., Baier, L. D., & Morrison, A. R. (1997). P38 mitogen-activated protein kinase down-regulates nitric oxide and up-regulates prostaglandin E2 biosynthesis stimulated by interleukin-1beta. The Journal of Biological Chemistry, 272(12), 8083-9.
Guan Z, Baier LD, Morrison AR. P38 Mitogen-activated Protein Kinase Down-regulates Nitric Oxide and Up-regulates Prostaglandin E2 Biosynthesis Stimulated By Interleukin-1beta. J Biol Chem. 1997 Mar 21;272(12):8083-9. PubMed PMID: 9065483.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - p38 mitogen-activated protein kinase down-regulates nitric oxide and up-regulates prostaglandin E2 biosynthesis stimulated by interleukin-1beta. AU - Guan,Z, AU - Baier,L D, AU - Morrison,A R, PY - 1997/3/21/pubmed PY - 1997/3/21/medline PY - 1997/3/21/entrez SP - 8083 EP - 9 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 272 IS - 12 N2 - The inflammatory cytokine interleukin 1beta (IL-1beta) induces both cyclooxygenase-2 (Cox-2) and the inducible nitric-oxide synthase (iNOS) with increases in the release of prostaglandins (PGs) and nitric oxide (NO) from glomerular mesangial cells. However, the intracellular signaling mechanisms by which IL-1beta induces iNOS and Cox-2 expression is obscure. Our current studies demonstrate that IL-1beta produces a rapid increase in p38 mitogen-activated protein kinase (MAPK) phosphorylation and activation. Serum starvation and SC68376, a drug which selectively inhibits p38 MAPK in mesangial cells, were used to investigate whether p38 MAPK contributes to the signaling mechanism of IL-1beta induction of NO and PG synthesis. Serum starvation and SC68376 selectively inhibited IL-1beta-induced activation of p38 MAPK. Both SC68376 and serum starvation enhanced NO biosynthesis by increasing iNOS mRNA expression, protein expression, and nitrite production. In contrast, both SC68376 and serum starvation suppressed PG release by inhibiting Cox-2 mRNA, protein expression, and PGE2 synthesis. These data demonstrate that IL-1beta phosphorylates and activates p38 MAPK in mesangial cells. The activation of p38 MAPK may provide a crucial signaling mechanism, which mediates the up-regulation of PG synthesis and the down-regulation of NO biosynthesis induced by IL-1beta. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/9065483/p38_mitogen_activated_protein_kinase_down_regulates_nitric_oxide_and_up_regulates_prostaglandin_E2_biosynthesis_stimulated_by_interleukin_1beta_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=9065483 DB - PRIME DP - Unbound Medicine ER -