PMID- 10542218 OWN - NLM STAT- MEDLINE DCOM- 19991213 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 45 DP - 1999 Nov 5 TI - trans-Retinoic acid blocks platelet-derived growth factor-BB-induced expression of the murine monocyte chemoattractant-1 gene by blocking the assembly of a promoter proximal Sp1 binding site. PG - 31909-16 AB - Proper regulation of the CC chemokine MCP-1 (monocyte chemoattractant protein-1) is important for normal inflammatory responses. MCP-1 is regulated by a wide variety of agents, including platelet-derived growth factor-BB (PDGF-BB) and tumor necrosis factor-alpha (TNF). Using both in vivo and in vitro assays, the elements required for expression between these two cytokines were compared. In vivo genomic footprinting showed that PDGF-BB induction occurred through the occupancy of the proximal regulatory region, and unlike TNF induction, no changes in the NF-kappaB binding, distal regulatory region occurred. Treatment of cells with trans-retinoic acid, an inhibitor of PDGF-BB activity, resulted in a 50% reduction in PDGF-BB-mediated induction and a concomitant block in the assembly of the proximal regulatory region. trans-Retinoic acid had minimal effect on TNF induction or promoter occupancy. An inhibitor of histone deacetylation was found to stimulate expression of MCP-1 in a manner that correlated with increased accessibility to the proximal regulatory region. These results show that the mechanisms of PDGF-BB and TNF activation of MCP-1 are distinct, although they both require the proximal regulatory region Sp1 binding site. The results also suggest that part of the mechanism used by both of these cytokines involves a process that regulates transcription factor access to the regulatory regions. FAU - Ping, D AU - Ping D AD - Department of Microbiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. FAU - Boekhoudt, G AU - Boekhoudt G FAU - Boss, J M AU - Boss JM LA - eng GR - CA74271/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Chemokine CCL2) RN - 0 (DNA-Binding Proteins) RN - 0 (Platelet-Derived Growth Factor) RN - 0 (Proto-Oncogene Proteins c-sis) RN - 0 (Sp1 Transcription Factor) RN - 0 (Transcription Factors) RN - 0 (Tumor Necrosis Factor-alpha) RN - 148710-94-5 (Sp3 Transcription Factor) RN - 1B56C968OA (Becaplermin) RN - 5688UTC01R (Tretinoin) SB - IM MH - 3T3 Cells MH - Animals MH - Becaplermin MH - Binding Sites MH - Chemokine CCL2/*genetics MH - DNA-Binding Proteins/metabolism MH - Electrophoresis, Polyacrylamide Gel MH - Fibroblasts/drug effects/metabolism MH - Mice MH - Platelet-Derived Growth Factor/*pharmacology MH - *Promoter Regions, Genetic MH - Proto-Oncogene Proteins c-sis MH - Sp1 Transcription Factor/*metabolism MH - Sp3 Transcription Factor MH - Transcription Factors/metabolism MH - Tretinoin/*pharmacology MH - Tumor Necrosis Factor-alpha/pharmacology MH - Zinc Fingers EDAT- 1999/11/05 00:00 MHDA- 1999/11/05 00:01 CRDT- 1999/11/05 00:00 PHST- 1999/11/05 00:00 [pubmed] PHST- 1999/11/05 00:01 [medline] PHST- 1999/11/05 00:00 [entrez] AID - S0021-9258(19)51506-X [pii] AID - 10.1074/jbc.274.45.31909 [doi] PST - ppublish SO - J Biol Chem. 1999 Nov 5;274(45):31909-16. doi: 10.1074/jbc.274.45.31909.