PMID- 23608488 OWN - NLM STAT- MEDLINE DCOM- 20130719 LR - 20211021 IS - 1090-2422 (Electronic) IS - 0014-4827 (Print) IS - 0014-4827 (Linking) VI - 319 IP - 10 DP - 2013 Jun 10 TI - IL-4 inhibition of IL-1 induced Matrix metalloproteinase-3 (MMP-3) expression in human fibroblasts involves decreased AP-1 activation via negative crosstalk involving of Jun N-terminal kinase (JNK). PG - 1398-408 LID - S0014-4827(13)00169-9 [pii] LID - 10.1016/j.yexcr.2013.04.010 [doi] AB - Matrix metalloproteinase-3 (MMP-3) over-expression is associated with tissue destruction in the context of chronic inflammation. Previous studies showed that IL-4 inhibits induction of MMP-3 by IL-1beta, and suggested that AP-1 might be involved. Here we show that IL-1 induced binding of transcription factor AP-1 to the MMP-3 promoter consists primarily of c-Jun, JunB, and c-Fos and that binding of c-Jun and c-Fos is inhibited by the combination of cytokines while binding of Jun B is not. Mutation of the AP-1 site in the MMP-3 promoter decreased the ability of IL-4 to inhibit its transcription in transfected MG-63 cells. Western blotting showed that both cytokines activate Jun N-terminal kinase (JNK), but with somewhat different kinetics, and that activation of JNK by both cytokines individually is inhibited by the combination. These results indicate that IL-4 inhibition of MMP-3 expression is associated with reduction of IL-1 induced binding of active forms of the AP-1 dimer, while less active JunB-containing dimers remain, and suggest that these changes are associated with decreased activation of JNK. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Chambers, Mariah AU - Chambers M AD - Department of Biochemistry and Molecular Biology, Philadelphia College of Osteopathic Medicine, 4170 City Avenue, Philadelphia, PA 19131, USA. FAU - Kirkpatrick, Garrett AU - Kirkpatrick G FAU - Evans, Michel AU - Evans M FAU - Gorski, Grzegorz AU - Gorski G FAU - Foster, Sara AU - Foster S FAU - Borghaei, Ruth C AU - Borghaei RC LA - eng GR - R15 DE016277/DE/NIDCR NIH HHS/United States GR - R15DE16277/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130419 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (FOSB protein, human) RN - 0 (Interleukin-1) RN - 0 (JunB protein, human) RN - 0 (JunD protein, human) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factor AP-1) RN - 0 (Transcription Factors) RN - 207137-56-2 (Interleukin-4) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8) RN - EC 3.4.24.17 (MMP3 protein, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.24.7 (MMP1 protein, human) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Binding Sites MH - Blotting, Western MH - Cell Line, Tumor MH - Enzyme Activation MH - Fibroblasts/drug effects/enzymology/metabolism MH - Foreskin/cytology MH - Humans MH - Interleukin-1/*pharmacology MH - Interleukin-4/*pharmacology MH - Male MH - Matrix Metalloproteinase 1/genetics/metabolism MH - Matrix Metalloproteinase 3/genetics/*metabolism MH - Mitogen-Activated Protein Kinase 8/genetics/*metabolism MH - Periodontitis/enzymology/metabolism/pathology MH - Promoter Regions, Genetic MH - Protein Binding MH - Protein Multimerization MH - Proto-Oncogene Proteins c-fos/genetics/metabolism MH - Proto-Oncogene Proteins c-jun/genetics/metabolism MH - RNA, Messenger/genetics/metabolism MH - Transcription Factor AP-1/*metabolism MH - Transcription Factors/genetics/*metabolism MH - Transcriptional Activation MH - Transfection PMC - PMC3757497 MID - NIHMS470770 EDAT- 2013/04/24 06:00 MHDA- 2013/07/20 06:00 PMCR- 2014/06/10 CRDT- 2013/04/24 06:00 PHST- 2012/07/31 00:00 [received] PHST- 2013/04/01 00:00 [revised] PHST- 2013/04/05 00:00 [accepted] PHST- 2013/04/24 06:00 [entrez] PHST- 2013/04/24 06:00 [pubmed] PHST- 2013/07/20 06:00 [medline] PHST- 2014/06/10 00:00 [pmc-release] AID - S0014-4827(13)00169-9 [pii] AID - 10.1016/j.yexcr.2013.04.010 [doi] PST - ppublish SO - Exp Cell Res. 2013 Jun 10;319(10):1398-408. doi: 10.1016/j.yexcr.2013.04.010. Epub 2013 Apr 19.