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)

Document Type

Article

Publication Date

6-10-2013

Abstract

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-1β, 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.

Publication Title

Experimental Cell Research

Volume

319

Issue

10

First Page

1398

Last Page

1408

PubMed ID

23608488

Comments

This article was published in Experimental Cell Research. Volume 319, Issue 10, pages 1398-408.

The published version is available at http://dx.doi.org/10.1016/j.yexcr.2013.04.010

Copyright © 2013 Elsevier Inc

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