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Activation of p38, ERK1/2 and NIK pathways is required for IL-1beta and TNF-alpha-induced chemokine expression in human retinal pigment epithelial cells.
Exp Eye Res. 2001 Jul; 73(1):111-21.EE

Abstract

Chemokine secretion by human retinal pigment epithelium (hRPE) in response to IL-1beta and TNF-alpha occurs in infectious and noninfectious retinal diseases. In this study, the roles of p38 kinase and extracellular signal-regulated kinase (ERK) signaling pathways were investigated for IL-1beta- or TNF-alpha-induced IL-8 and MCP-1 secretion by hRPE cells. Treatment of hRPE cells with IL-1beta or TNF-alpha caused increased steady-state IL-8 and MCP-1 mRNA levels and protein secretion. Stimulation of hRPE with IL-1beta and TNF-alpha resulted in degradation of IkappaB-alpha, nuclear translocation of NF-kappaB, and prominent increases in p38 and ERK1/2 phosphorylation for as little as 3 min. The induced IL-8 and MCP-1 mRNA and proteins were partially suppressed by U0126, a specific MEK inhibitor, and by SB202190, a selective p38 inhibitor. This induction was completely blocked by simultaneous administration of the two drugs or by incubation with inhibitors for activation of NF-kappaB such as BAY11-7085, CAPE, and parthenolide. These results suggest that co-activation of MEK/ERK and p38 pathways as well as activation of NIK pathway are essential for IL-1beta- and TNF-alpha-stimulation of IL-8 and MCP-1 gene expression in hRPE cells. Furthermore, co-administration of U0126 and SB202190 did not affect the induced degradation of IkappaB-alpha and NF-kappaB nuclear translocation, indicating that NF-kappaB is activated by IL-1beta and TNF-alpha independently of activation of MEK/MAPK and p38 pathways in hRPE cells.

Authors+Show Affiliations

Department of Ophthalmology, University of Michigan, Ann Arbor, MI 48105, U.S.A.No affiliation info availableNo 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

11428868

Citation

Bian, Z M., et al. "Activation of P38, ERK1/2 and NIK Pathways Is Required for IL-1beta and TNF-alpha-induced Chemokine Expression in Human Retinal Pigment Epithelial Cells." Experimental Eye Research, vol. 73, no. 1, 2001, pp. 111-21.
Bian ZM, Elner SG, Yoshida A, et al. Activation of p38, ERK1/2 and NIK pathways is required for IL-1beta and TNF-alpha-induced chemokine expression in human retinal pigment epithelial cells. Exp Eye Res. 2001;73(1):111-21.
Bian, Z. M., Elner, S. G., Yoshida, A., Kunkel, S. L., Su, J., & Elner, V. M. (2001). Activation of p38, ERK1/2 and NIK pathways is required for IL-1beta and TNF-alpha-induced chemokine expression in human retinal pigment epithelial cells. Experimental Eye Research, 73(1), 111-21.
Bian ZM, et al. Activation of P38, ERK1/2 and NIK Pathways Is Required for IL-1beta and TNF-alpha-induced Chemokine Expression in Human Retinal Pigment Epithelial Cells. Exp Eye Res. 2001;73(1):111-21. PubMed PMID: 11428868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of p38, ERK1/2 and NIK pathways is required for IL-1beta and TNF-alpha-induced chemokine expression in human retinal pigment epithelial cells. AU - Bian,Z M, AU - Elner,S G, AU - Yoshida,A, AU - Kunkel,S L, AU - Su,J, AU - Elner,V M, PY - 2001/6/29/pubmed PY - 2001/10/5/medline PY - 2001/6/29/entrez SP - 111 EP - 21 JF - Experimental eye research JO - Exp Eye Res VL - 73 IS - 1 N2 - Chemokine secretion by human retinal pigment epithelium (hRPE) in response to IL-1beta and TNF-alpha occurs in infectious and noninfectious retinal diseases. In this study, the roles of p38 kinase and extracellular signal-regulated kinase (ERK) signaling pathways were investigated for IL-1beta- or TNF-alpha-induced IL-8 and MCP-1 secretion by hRPE cells. Treatment of hRPE cells with IL-1beta or TNF-alpha caused increased steady-state IL-8 and MCP-1 mRNA levels and protein secretion. Stimulation of hRPE with IL-1beta and TNF-alpha resulted in degradation of IkappaB-alpha, nuclear translocation of NF-kappaB, and prominent increases in p38 and ERK1/2 phosphorylation for as little as 3 min. The induced IL-8 and MCP-1 mRNA and proteins were partially suppressed by U0126, a specific MEK inhibitor, and by SB202190, a selective p38 inhibitor. This induction was completely blocked by simultaneous administration of the two drugs or by incubation with inhibitors for activation of NF-kappaB such as BAY11-7085, CAPE, and parthenolide. These results suggest that co-activation of MEK/ERK and p38 pathways as well as activation of NIK pathway are essential for IL-1beta- and TNF-alpha-stimulation of IL-8 and MCP-1 gene expression in hRPE cells. Furthermore, co-administration of U0126 and SB202190 did not affect the induced degradation of IkappaB-alpha and NF-kappaB nuclear translocation, indicating that NF-kappaB is activated by IL-1beta and TNF-alpha independently of activation of MEK/MAPK and p38 pathways in hRPE cells. SN - 0014-4835 UR - https://www.unboundmedicine.com/medline/citation/11428868/Activation_of_p38_ERK1/2_and_NIK_pathways_is_required_for_IL_1beta_and_TNF_alpha_induced_chemokine_expression_in_human_retinal_pigment_epithelial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(01)91019-X DB - PRIME DP - Unbound Medicine ER -