RGD Reference Report - Suppression of constitutive but not Il-1beta-inducible expression of monocyte chemoattractant protein-1 in mesangial cells by retinoic acids: intervention in the activator protein-1 pathway. - Rat Genome Database
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Suppression of constitutive but not Il-1beta-inducible expression of monocyte chemoattractant protein-1 in mesangial cells by retinoic acids: intervention in the activator protein-1 pathway.

Authors: Lucio-Cazana, J  Nakayama, K  Xu, Q  Konta, T  Moreno-Manzano, V  Furusu, A  Kitamura, M 
Citation: Lucio-Cazana J, etal., J Am Soc Nephrol. 2001 Apr;12(4):688-94.
RGD ID: 8549584
Pubmed: (View Article at PubMed) PMID:11274229

Retinoic acid regulates a wide range of biologic processes, including inflammation. This study investigated the effect of all-trans-retinoic acid (t-RA) on the constitutive and cytokine-inducible expression of monocyte chemoattractant protein 1 (MCP-1) in rat mesangial cells. Serum-deprived mesangial cells exhibited substantial levels of MCP-1 mRNA, and the expression was markedly upregulated by interleukin-1beta (IL-1beta). Pretreatment with t-RA abrogated the constitutive mRNA expression but did not inhibit the IL-1beta-inducible expression. The similar effects were observed by 9-cis-RA. The suppressive effect of t-RA required retinoic acid receptors. t-RA did not affect the stability of MCP-1 mRNA, indicating that its suppressive effect was at the transcriptional level. Experiments that used pharmacologic and genetic inhibitors showed that the IL-1beta-inducible MCP-1 expression was dependent on nuclear factor-kappaB (NF-kappaB) and independent of activator protein 1 (AP-1). In contrast, the constitutive expression of MCP-1 was dependent on both NF-kappaB and AP-1. t-RA substantially inhibited the constitutive activity of AP-1 but did not inhibit NF-kappaB activity in mesangial cells. These data suggested that (1) constitutive and IL-1beta-inducible expression of MCP-1 was differently regulated by AP-1 and NF-kappaB and (2) t-RA inhibited selectively the constitutive expression of MCP-1 via intervention in the AP-1 pathway.

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Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)


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