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Thrombin stimulates RPE cell motility by PKC-zeta- and NF-kappaB-dependent gene expression of MCP-1 and CINC-1/GRO chemokines.
J Cell Biochem. 2010 Jul 01; 110(4):948-67.JC

Abstract

Retinal pigment epithelial cells (RPE) are the major cell type involved in the pathogenesis of proliferative vitreoretinopathy (PVR), which involves the epithelial-mesenchymal transition, proliferation, and directional migration of transformed RPE cells to the vitreous upon RPE exposure to serum components, thrombin among them. Although the aqueous humor and vitreous of PVR patients contain high levels of chemokines, their possible involvement in PVR development has not been explored. We here analyzed the effect of thrombin on chemokine gene expression and its correlation with RPE cell migration using rat RPE cells in culture as a model system. We demonstrated that thrombin induces RPE cell migration through the dose-dependent stimulation of MCP1 and GRO expression/release, and the autocrine activation of CXCR-2 and CCR-2 chemokine receptors. Whereas inhibition of CXCR2 by Sb-225002 and of CCR2 by Rs-504393 partially prevented hirudin-sensitive cell migration, the joint inhibition of these receptors abolished thrombin effect, suggesting the contribution of distinct but coincident mechanisms. Thrombin effects were not modified by Ro-32-0432 inhibition of conventional/novel PKC isoenzymes or by the MAPkinase pathway inhibitor U0126. MCP1 and GRO expression/secretion, and cell migration were completely prevented by the inhibitory PKC-zeta pseudosubstrate and by the nuclear factor-kappa B (NF-kappaB) inhibitor BAY11-7082, but not by wortmannin inhibition of PI3K. Results show that signaling pathways leading to RPE cell migration differ from the MEK-ERK-PI3K-mediated promotion RPE of cell proliferation, both of which concur at the activation of PKC-zeta.

Authors+Show Affiliations

División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Coyoacan, México, DF.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20564194

Citation

Palma-Nicolás, José Prisco, et al. "Thrombin Stimulates RPE Cell Motility By PKC-zeta- and NF-kappaB-dependent Gene Expression of MCP-1 and CINC-1/GRO Chemokines." Journal of Cellular Biochemistry, vol. 110, no. 4, 2010, pp. 948-67.
Palma-Nicolás JP, López E, López-Colomé AM. Thrombin stimulates RPE cell motility by PKC-zeta- and NF-kappaB-dependent gene expression of MCP-1 and CINC-1/GRO chemokines. J Cell Biochem. 2010;110(4):948-67.
Palma-Nicolás, J. P., López, E., & López-Colomé, A. M. (2010). Thrombin stimulates RPE cell motility by PKC-zeta- and NF-kappaB-dependent gene expression of MCP-1 and CINC-1/GRO chemokines. Journal of Cellular Biochemistry, 110(4), 948-67. https://doi.org/10.1002/jcb.22608
Palma-Nicolás JP, López E, López-Colomé AM. Thrombin Stimulates RPE Cell Motility By PKC-zeta- and NF-kappaB-dependent Gene Expression of MCP-1 and CINC-1/GRO Chemokines. J Cell Biochem. 2010 Jul 1;110(4):948-67. PubMed PMID: 20564194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thrombin stimulates RPE cell motility by PKC-zeta- and NF-kappaB-dependent gene expression of MCP-1 and CINC-1/GRO chemokines. AU - Palma-Nicolás,José Prisco, AU - López,Edith, AU - López-Colomé,Ana María, PY - 2010/6/22/entrez PY - 2010/6/22/pubmed PY - 2010/11/3/medline SP - 948 EP - 67 JF - Journal of cellular biochemistry JO - J. Cell. Biochem. VL - 110 IS - 4 N2 - Retinal pigment epithelial cells (RPE) are the major cell type involved in the pathogenesis of proliferative vitreoretinopathy (PVR), which involves the epithelial-mesenchymal transition, proliferation, and directional migration of transformed RPE cells to the vitreous upon RPE exposure to serum components, thrombin among them. Although the aqueous humor and vitreous of PVR patients contain high levels of chemokines, their possible involvement in PVR development has not been explored. We here analyzed the effect of thrombin on chemokine gene expression and its correlation with RPE cell migration using rat RPE cells in culture as a model system. We demonstrated that thrombin induces RPE cell migration through the dose-dependent stimulation of MCP1 and GRO expression/release, and the autocrine activation of CXCR-2 and CCR-2 chemokine receptors. Whereas inhibition of CXCR2 by Sb-225002 and of CCR2 by Rs-504393 partially prevented hirudin-sensitive cell migration, the joint inhibition of these receptors abolished thrombin effect, suggesting the contribution of distinct but coincident mechanisms. Thrombin effects were not modified by Ro-32-0432 inhibition of conventional/novel PKC isoenzymes or by the MAPkinase pathway inhibitor U0126. MCP1 and GRO expression/secretion, and cell migration were completely prevented by the inhibitory PKC-zeta pseudosubstrate and by the nuclear factor-kappa B (NF-kappaB) inhibitor BAY11-7082, but not by wortmannin inhibition of PI3K. Results show that signaling pathways leading to RPE cell migration differ from the MEK-ERK-PI3K-mediated promotion RPE of cell proliferation, both of which concur at the activation of PKC-zeta. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/20564194/Thrombin_stimulates_RPE_cell_motility_by_PKC_zeta__and_NF_kappaB_dependent_gene_expression_of_MCP_1_and_CINC_1/GRO_chemokines_ L2 - https://doi.org/10.1002/jcb.22608 DB - PRIME DP - Unbound Medicine ER -