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Tumor necrosis factor-alpha induction of endothelial ephrin A1 expression is mediated by a p38 MAPK- and SAPK/JNK-dependent but nuclear factor-kappa B-independent mechanism.
J Biol Chem. 2001 Apr 27; 276(17):13771-7.JB

Abstract

Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that induces a broad spectrum of responses including angiogenesis. Angiogenesis promoted by TNF-alpha is mediated, at least in part, by ephrin A1, a member of the ligand family for Eph receptor tyrosine kinases. Although TNF-alpha induces ephrin A1 expression in endothelial cells, the signaling pathways mediating ephrin A1 induction remain unknown. In this study, we investigated the signaling mechanisms of TNF-alpha-dependent induction of ephrin A1 in endothelial cells. Both TNFR1 and TNFR2 appear to be involved in regulating ephrin A1 expression in endothelial cells, because neutralizing antibodies to either TNFR1 or TNFR2 inhibited TNF-alpha-induced ephrin A1 expression. Inhibition of nuclear factor-kappaB (NF-kappaB) activation by a trans-dominant inhibitory isoform of mutant IkappaBalpha did not affect ephrin A1 induction, suggesting that NF-kappaB proteins are not major regulators of ephrin A1 expression. In contrast, ephrin A1 induction was blocked by inhibition of p38 mitogen-activated protein kinase (MAPK) or SAPK/JNK, but not p42/44 MAPK, using either selective chemical inhibitors or dominant-negative forms of p38 MAPK or TNF receptor-associated factor 2. These findings indicate that TNF-alpha-induced ephrin A1 expression is mediated through JNK and p38 MAPK signaling pathways. Taken together, the results of our study demonstrated that induction of ephrin A1 in endothelial cells by TNF-alpha is mediated through both p38 MAPK and SAPK/JNK, but not p42/44 MAPK or NF-kappaB, pathways.

Authors+Show Affiliations

Department of Cell Biology, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA.No 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

11278471

Citation

Cheng, N, and J Chen. "Tumor Necrosis Factor-alpha Induction of Endothelial Ephrin A1 Expression Is Mediated By a P38 MAPK- and SAPK/JNK-dependent but Nuclear Factor-kappa B-independent Mechanism." The Journal of Biological Chemistry, vol. 276, no. 17, 2001, pp. 13771-7.
Cheng N, Chen J. Tumor necrosis factor-alpha induction of endothelial ephrin A1 expression is mediated by a p38 MAPK- and SAPK/JNK-dependent but nuclear factor-kappa B-independent mechanism. J Biol Chem. 2001;276(17):13771-7.
Cheng, N., & Chen, J. (2001). Tumor necrosis factor-alpha induction of endothelial ephrin A1 expression is mediated by a p38 MAPK- and SAPK/JNK-dependent but nuclear factor-kappa B-independent mechanism. The Journal of Biological Chemistry, 276(17), 13771-7.
Cheng N, Chen J. Tumor Necrosis Factor-alpha Induction of Endothelial Ephrin A1 Expression Is Mediated By a P38 MAPK- and SAPK/JNK-dependent but Nuclear Factor-kappa B-independent Mechanism. J Biol Chem. 2001 Apr 27;276(17):13771-7. PubMed PMID: 11278471.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor necrosis factor-alpha induction of endothelial ephrin A1 expression is mediated by a p38 MAPK- and SAPK/JNK-dependent but nuclear factor-kappa B-independent mechanism. AU - Cheng,N, AU - Chen,J, Y1 - 2001/02/02/ PY - 2001/3/30/pubmed PY - 2001/6/15/medline PY - 2001/3/30/entrez SP - 13771 EP - 7 JF - The Journal of biological chemistry JO - J Biol Chem VL - 276 IS - 17 N2 - Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that induces a broad spectrum of responses including angiogenesis. Angiogenesis promoted by TNF-alpha is mediated, at least in part, by ephrin A1, a member of the ligand family for Eph receptor tyrosine kinases. Although TNF-alpha induces ephrin A1 expression in endothelial cells, the signaling pathways mediating ephrin A1 induction remain unknown. In this study, we investigated the signaling mechanisms of TNF-alpha-dependent induction of ephrin A1 in endothelial cells. Both TNFR1 and TNFR2 appear to be involved in regulating ephrin A1 expression in endothelial cells, because neutralizing antibodies to either TNFR1 or TNFR2 inhibited TNF-alpha-induced ephrin A1 expression. Inhibition of nuclear factor-kappaB (NF-kappaB) activation by a trans-dominant inhibitory isoform of mutant IkappaBalpha did not affect ephrin A1 induction, suggesting that NF-kappaB proteins are not major regulators of ephrin A1 expression. In contrast, ephrin A1 induction was blocked by inhibition of p38 mitogen-activated protein kinase (MAPK) or SAPK/JNK, but not p42/44 MAPK, using either selective chemical inhibitors or dominant-negative forms of p38 MAPK or TNF receptor-associated factor 2. These findings indicate that TNF-alpha-induced ephrin A1 expression is mediated through JNK and p38 MAPK signaling pathways. Taken together, the results of our study demonstrated that induction of ephrin A1 in endothelial cells by TNF-alpha is mediated through both p38 MAPK and SAPK/JNK, but not p42/44 MAPK or NF-kappaB, pathways. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/11278471/Tumor_necrosis_factor_alpha_induction_of_endothelial_ephrin_A1_expression_is_mediated_by_a_p38_MAPK__and_SAPK/JNK_dependent_but_nuclear_factor_kappa_B_independent_mechanism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)78820-4 DB - PRIME DP - Unbound Medicine ER -