Gene interactions and pathways from curated databases and text-mining
Am J Physiol Heart Circ Physiol 2007, PMID: 17921324

IL-17 stimulates MMP-1 expression in primary human cardiac fibroblasts via p38 MAPK- and ERK1/2-dependent C/EBP-beta , NF-kappaB, and AP-1 activation.

Cortez, Dolores M; Feldman, Marc D; Mummidi, Srinivas; Valente, Anthony J; Steffensen, Bjorn; Vincenti, Matthew; Barnes, Jeffrey L; Chandrasekar, Bysani

Matrix metalloproteinases (MMPs) degrade collagen and mediate tissue remodeling. The novel cytokine IL-17 is expressed during various inflammatory conditions and modulates MMP expression. We investigated the effect of IL-17 on MMP-1 expression in primary human cardiac fibroblasts (HCF) and delineated the signaling pathways involved. HCF were treated with recombinant human IL-17. MMP-1 expression was analyzed by Northern blotting, RT-quantitative PCR, Western blotting, and ELISA; transcriptional induction and transcription factor binding by EMSA, ELISA, and reporter assay; and p38 MAPK and ERK1/2 activation by protein kinase assays and Western blotting. Signal transduction pathways were investigated using pharmacological inhibitors, small interfering RNA (siRNA), and adenoviral dominant-negative expression vectors. IL-17 stimulated MMP-1 gene transcription, net mRNA levels, protein, and promoter-reporter activity in HCF. This response was blocked by IL-17 receptor-Fc chimera and IL-17 receptor antibodies, but not by IL-6, TNF-alpha, or IL-1beta antibodies. IL-17-stimulated type I collagenase activity was inhibited by the MMP inhibitor GM-6001 and by siRNA-mediated MMP-1 knockdown. IL-17 stimulated activator protein-1 [AP-1 (c-Fos, c-Jun, and Fra-1)], NF-kappaB (p50 and p65), and CCAAT enhancer-binding protein (C/EBP)-beta DNA binding and reporter gene activities, effects attenuated by antisense oligonucleotides, siRNA-mediated knockdown, or expression of dominant-negative signaling proteins. Inhibition of AP-1, NF-kappaB, or C/EBP activation attenuated IL-17-stimulated MMP-1 expression. IL-17 induced p38 MAPK and ERK1/2 activation, and inhibition by SB-203580 and PD-98059 blunted IL-17-mediated transcription factor activation and MMP-1 expression. Our data indicate that IL-17 induces MMP-1 in human cardiac fibroblasts directly via p38 MAPK- and ERK-dependent AP-1, NF-kappaB, and C/EBP-beta activation and suggest that IL-17 may play a critical role in myocardial remodeling.

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Text Mining Data

C/EBP-beta → ERK1/2: " IL-17 stimulates MMP-1 expression in primary human cardiac fibroblasts via p38 MAPK- and ERK1/2 dependent C/EBP-beta , NF-kappaB, and AP-1 activation "

MMP-1 → IL-17: " IL-17 stimulates MMP-1 expression in primary human cardiac fibroblasts via p38 MAPK- and ERK1/2 dependent C/EBP-beta, NF-kappaB, and AP-1 activation "

MMP-1 — IL-17: " We investigated the effect of IL-17 on MMP-1 expression in primary human cardiac fibroblasts (HCF) and delineated the signaling pathways involved "

activator protein-1 → IL-17: " IL-17 stimulated activator protein-1 [ AP-1 ( c-Fos, c-Jun, and Fra-1 ) ], NF-kappaB ( p50 and p65 ), and CCAAT enhancer binding protein (C/EBP)-beta DNA binding and reporter gene activities, effects attenuated by antisense oligonucleotides, siRNA mediated knockdown, or expression of dominant negative signaling proteins "

NF-kappaB → IL-17: " IL-17 stimulated activator protein-1 [ AP-1 ( c-Fos, c-Jun, and Fra-1 ) ], NF-kappaB ( p50 and p65 ), and CCAAT enhancer binding protein (C/EBP)-beta DNA binding and reporter gene activities, effects attenuated by antisense oligonucleotides, siRNA mediated knockdown, or expression of dominant negative signaling proteins "

MMP-1 → C/EBP: " Inhibition of AP-1, NF-kappaB, or C/EBP activation attenuated IL-17 stimulated MMP-1 expression "

MMP-1 → AP-1: " Inhibition of AP-1 , NF-kappaB, or C/EBP activation attenuated IL-17 stimulated MMP-1 expression "

MMP-1 → IL-17: " Inhibition of AP-1, NF-kappaB, or C/EBP activation attenuated IL-17 stimulated MMP-1 expression "

MMP-1 → NF-kappaB: " Inhibition of AP-1, NF-kappaB , or C/EBP activation attenuated IL-17 stimulated MMP-1 expression "

MAPK → IL-17: " IL-17 induced p38 MAPK and ERK1/2 activation, and inhibition by SB-203580 and PD-98059 blunted IL-17 mediated transcription factor activation and MMP-1 expression "

ERK1/2 → transcription factor: " IL-17 induced p38 MAPK and ERK1/2 activation , and inhibition by SB-203580 and PD-98059 blunted IL-17 mediated transcription factor activation and MMP-1 expression "

ERK1/2 → IL-17: " IL-17 induced p38 MAPK and ERK1/2 activation, and inhibition by SB-203580 and PD-98059 blunted IL-17 mediated transcription factor activation and MMP-1 expression "

MMP-1 → IL-17: " IL-17 induced p38 MAPK and ERK1/2 activation, and inhibition by SB-203580 and PD-98059 blunted IL-17 mediated transcription factor activation and MMP-1 expression "

C/EBP-beta → ERK: " Our data indicate that IL-17 induces MMP-1 in human cardiac fibroblasts directly via p38 MAPK- and ERK dependent AP-1, NF-kappaB, and C/EBP-beta activation and suggest that IL-17 may play a critical role in myocardial remodeling "

AP-1 → ERK: " Our data indicate that IL-17 induces MMP-1 in human cardiac fibroblasts directly via p38 MAPK- and ERK dependent AP-1 , NF-kappaB, and C/EBP-beta activation and suggest that IL-17 may play a critical role in myocardial remodeling "

MMP-1 → IL-17: " Our data indicate that IL-17 induces MMP-1 in human cardiac fibroblasts directly via p38 MAPK- and ERK dependent AP-1, NF-kappaB, and C/EBP-beta activation and suggest that IL-17 may play a critical role in myocardial remodeling "

NF-kappaB → ERK: " Our data indicate that IL-17 induces MMP-1 in human cardiac fibroblasts directly via p38 MAPK- and ERK dependent AP-1, NF-kappaB , and C/EBP-beta activation and suggest that IL-17 may play a critical role in myocardial remodeling "

Manually curated Databases

No curated data.