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Interleukin-1beta-induced cyclooxygenase-2 expression requires activation of both c-Jun NH2-terminal kinase and p38 MAPK signal pathways in rat renal mesangial cells.
J Biol Chem. 1998 Oct 30; 273(44):28670-6.JB

Abstract

The inflammatory cytokine interleukin-1beta (IL-1beta) induces cyclooxygenase-2 (Cox-2) expression with a concomitant release of prostaglandins from glomerular mesangial cells. We reported previously that IL-1beta rapidly activates the c-Jun NH2-terminal/stress-activated protein kinases (JNK/SAPK) and p38 mitogen-activated protein kinase (MAPK) and also induces Cox-2 expression and prostaglandin E2 (PGE2) production. The current study demonstrates that overexpression of the dominant negative form of JNK1 or p54 JNK2/SAPKbeta reduces Cox-2 expression and PGE2 production stimulated by IL-1beta. Similarly, overexpression of the kinase-dead form of p38 MAPK also inhibits IL-1beta-induced Cox-2 expression and PGE2 production. These results suggest that activation of both JNK/SAPK and p38 MAPK is required for Cox-2 expression after IL-1beta activation. Furthermore, our experiments confirm that IL-1beta activates MAP kinase kinase-4 (MKK4)/SEK1, MKK3, and MKK6 in renal mesangial cells. Overexpression of the dominant negative form of MKK4/SEK1 decreases IL-1beta- induced Cox-2 expression with inhibition of both JNK/SAPK and p38 MAPK phosphorylation. Overexpression of the kinase-dead form of MKK3 or MKK6 demonstrated that either of these two mutant kinases inhibited IL-1beta-induced p38 MAPK phosphorylation and Cox-2 expression but not JNK/SAPK phosphorylation and activation. This study suggests that the activation of both JNK/SAPK and p38 MAPK signaling cascades is required for IL-1beta-induced Cox-2 expression and PGE2 synthesis.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

9786861

Citation

Guan, Z, et al. "Interleukin-1beta-induced Cyclooxygenase-2 Expression Requires Activation of Both c-Jun NH2-terminal Kinase and P38 MAPK Signal Pathways in Rat Renal Mesangial Cells." The Journal of Biological Chemistry, vol. 273, no. 44, 1998, pp. 28670-6.
Guan Z, Buckman SY, Miller BW, et al. Interleukin-1beta-induced cyclooxygenase-2 expression requires activation of both c-Jun NH2-terminal kinase and p38 MAPK signal pathways in rat renal mesangial cells. J Biol Chem. 1998;273(44):28670-6.
Guan, Z., Buckman, S. Y., Miller, B. W., Springer, L. D., & Morrison, A. R. (1998). Interleukin-1beta-induced cyclooxygenase-2 expression requires activation of both c-Jun NH2-terminal kinase and p38 MAPK signal pathways in rat renal mesangial cells. The Journal of Biological Chemistry, 273(44), 28670-6.
Guan Z, et al. Interleukin-1beta-induced Cyclooxygenase-2 Expression Requires Activation of Both c-Jun NH2-terminal Kinase and P38 MAPK Signal Pathways in Rat Renal Mesangial Cells. J Biol Chem. 1998 Oct 30;273(44):28670-6. PubMed PMID: 9786861.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-1beta-induced cyclooxygenase-2 expression requires activation of both c-Jun NH2-terminal kinase and p38 MAPK signal pathways in rat renal mesangial cells. AU - Guan,Z, AU - Buckman,S Y, AU - Miller,B W, AU - Springer,L D, AU - Morrison,A R, PY - 1998/10/24/pubmed PY - 1998/10/24/medline PY - 1998/10/24/entrez SP - 28670 EP - 6 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 273 IS - 44 N2 - The inflammatory cytokine interleukin-1beta (IL-1beta) induces cyclooxygenase-2 (Cox-2) expression with a concomitant release of prostaglandins from glomerular mesangial cells. We reported previously that IL-1beta rapidly activates the c-Jun NH2-terminal/stress-activated protein kinases (JNK/SAPK) and p38 mitogen-activated protein kinase (MAPK) and also induces Cox-2 expression and prostaglandin E2 (PGE2) production. The current study demonstrates that overexpression of the dominant negative form of JNK1 or p54 JNK2/SAPKbeta reduces Cox-2 expression and PGE2 production stimulated by IL-1beta. Similarly, overexpression of the kinase-dead form of p38 MAPK also inhibits IL-1beta-induced Cox-2 expression and PGE2 production. These results suggest that activation of both JNK/SAPK and p38 MAPK is required for Cox-2 expression after IL-1beta activation. Furthermore, our experiments confirm that IL-1beta activates MAP kinase kinase-4 (MKK4)/SEK1, MKK3, and MKK6 in renal mesangial cells. Overexpression of the dominant negative form of MKK4/SEK1 decreases IL-1beta- induced Cox-2 expression with inhibition of both JNK/SAPK and p38 MAPK phosphorylation. Overexpression of the kinase-dead form of MKK3 or MKK6 demonstrated that either of these two mutant kinases inhibited IL-1beta-induced p38 MAPK phosphorylation and Cox-2 expression but not JNK/SAPK phosphorylation and activation. This study suggests that the activation of both JNK/SAPK and p38 MAPK signaling cascades is required for IL-1beta-induced Cox-2 expression and PGE2 synthesis. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/9786861/Interleukin_1beta_induced_cyclooxygenase_2_expression_requires_activation_of_both_c_Jun_NH2_terminal_kinase_and_p38_MAPK_signal_pathways_in_rat_renal_mesangial_cells_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=9786861 DB - PRIME DP - Unbound Medicine ER -