c-Rel and p65 trans-activate the monocyte chemoattractant protein-1 gene in interleukin-1 stimulated mesangial cells

Citation
E. Stylianou et al., c-Rel and p65 trans-activate the monocyte chemoattractant protein-1 gene in interleukin-1 stimulated mesangial cells, KIDNEY INT, 56(3), 1999, pp. 873-882
Citations number
41
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
KIDNEY INTERNATIONAL
ISSN journal
00852538 → ACNP
Volume
56
Issue
3
Year of publication
1999
Pages
873 - 882
Database
ISI
SICI code
0085-2538(199909)56:3<873:CAPTTM>2.0.ZU;2-P
Abstract
Background. The chemokine monocyte chemoattractant protein-1 (MCP-1) is sec reted by human glomerular mesangial cells in response to interleukin-l (IL- I) and has a central role in amplifying the inflammatory response during gl omerulonephritis. However, the mechanism by which IL-1 regulates its transc ription is not understood. Specific members of the nuclear factor kappa B/r el (NF-kappa B) proteins may regulate MCP-1 expression in a stimulus- and t issue-specific manner. Methods. Electrophoretic mobility shift assays and Western blot analysis ch aracterized the members of the NF-kappa B family that bound the two NF-kapp a B sites of the MCP-1 enhancer (Al and A2) in vitro. Trans-activation of t he MCP-1 gene was investigated by transfer of the MCP-1 enhancer DNA to mes angial cells. Result. Primary human mesangial cells contained in addition to p50 (NF-kapp a B1) and p65 (Rel A) NF-kappa B proteins. the oncoprotein c-rel, and Rel B , but not p52 (NF-kappa B2). IL-1 induced c-rel to form a complex with p65, which bound the MCP-1 A2 site but not the Al Or IL-6 NF-kappa B sites in v itro. IL-1 up-regulated transfected MCP-1 enhancer activity. Cotransfer of the MCP-1 enhancer together with individual members of the NF-kappa B famil y showed that the heterodimer c-relp65 or (p65)(2) can selectively trans-ac tivate the MCP-1 gene via its Al and A2 sites in mesangial cells. Conclusions. This study demonstrates for the first time that the c-rel onco protein can enhance MCP-1 transcription in mesangial cells and suggests tha t it may have an important role in amplifying gene expression in the inflam ed glomerulus.