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Gene interactions and pathways from curated databases and text-mining
Exp Cell Res 2013, PMID: 23608488

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).

Chambers, Mariah; Kirkpatrick, Garrett; Evans, Michel; Gorski, Grzegorz; Foster, Sara; Borghaei, Ruth C

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.

Diseases/Pathways annotated by Medline MESH: Periodontitis
Document information provided by NCBI PubMed

Text Mining Data

IL-1 ⊣ AP-1: " 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) "

IL-1 ⊣ IL-4: " 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) "

IL-4 ⊣ AP-1: " 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) "

IL-1 → Matrix Metalloproteinase-3 (MMP-3): " 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) "

MMP-3 ⊣ IL-4: " Previous studies showed that IL-4 inhibits induction of MMP-3 by IL-1ß, and suggested that AP-1 might be involved "

AP-1 ⊣ c-Fos: " 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 "

c-Fos ⊣ IL-1: " 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 "

c-Fos ⊣ MMP-3: " 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 "

c-Jun ⊣ AP-1: " 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 "

c-Jun ⊣ IL-1: " 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 "

c-Jun ⊣ MMP-3: " 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 "

AP-1 → IL-1: " 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 "

MMP-3 → IL-1: " 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 "

MMP-3 ⊣ IL-4: " 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 "

Manually curated Databases

No curated data.