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Matrix metalloproteinase-13 expression in IL-1β-treated chondrocytes by activation of the p38 MAPK/c-Fos/AP-1 and JAK/STAT pathways.
Arch Pharm Res. 2011 Jan; 34(1):109-17.AP

Abstract

Matrix metalloproteinase-13 (MMP-13, mammalian collagenase) degrades the cartilage matrix in pathological conditions such as osteoarthritis. Here, to establish the signaling pathway to MMP-13 induction, effects of mitogen-activated protein kinase (MAPK) pathway and the possibility of some other signaling pathways involved are investigated in interleukin-1β (IL-1β)-treated human chondrosarcoma cell line, SW1353 cells. IL-1β (10 ng/mL) treatment induced MMP-13 in SW1353 cells, with concomitant activation of nuclear factor-κB, activator protein-1 (AP-1) and MAPKs, including extracellular signal-regulated protein kinase, p38 MAPK and c-Jun N-terminal kinase. Among these MAPKs, only p38 MAPK inhibitor (SB203580) blocked MMP-13 induction and AP-1 activation in IL-1β-treated SW1353 cells. SB203580 also inhibited c-Fos translocation to the nucleus (but not c-Jun). Importantly, IL-1β treatment induced Janus kinase 2 (JAK2) and signal transducer and activator of transcription 1/2 (STAT1/2) activation. The JAK2 inhibitor (AG490) blocked STAT1/2 activation as well as MMP-13 induction in IL-1β-treated SW1353 cells. STAT1/2 siRNA transfection also reduced MMP-13 expression levels. Thus, from the present study, it is concluded that p38 MAPK/c-Fos/AP-1 and JAK2/STAT1/2 are involved in MMP-13 induction of IL-1β-treated human chondrocytes, SW1353 cells. Blocking these signaling pathways may have chondroprotective effects in cartilage degeneration.

Authors+Show Affiliations

College of Pharmacy, Kangwon National University, Chunchon, Korea.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21468922

Citation

Lim, Hyun, and Hyun Pyo Kim. "Matrix Metalloproteinase-13 Expression in IL-1β-treated Chondrocytes By Activation of the P38 MAPK/c-Fos/AP-1 and JAK/STAT Pathways." Archives of Pharmacal Research, vol. 34, no. 1, 2011, pp. 109-17.
Lim H, Kim HP. Matrix metalloproteinase-13 expression in IL-1β-treated chondrocytes by activation of the p38 MAPK/c-Fos/AP-1 and JAK/STAT pathways. Arch Pharm Res. 2011;34(1):109-17.
Lim, H., & Kim, H. P. (2011). Matrix metalloproteinase-13 expression in IL-1β-treated chondrocytes by activation of the p38 MAPK/c-Fos/AP-1 and JAK/STAT pathways. Archives of Pharmacal Research, 34(1), 109-17. https://doi.org/10.1007/s12272-011-0113-4
Lim H, Kim HP. Matrix Metalloproteinase-13 Expression in IL-1β-treated Chondrocytes By Activation of the P38 MAPK/c-Fos/AP-1 and JAK/STAT Pathways. Arch Pharm Res. 2011;34(1):109-17. PubMed PMID: 21468922.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Matrix metalloproteinase-13 expression in IL-1β-treated chondrocytes by activation of the p38 MAPK/c-Fos/AP-1 and JAK/STAT pathways. AU - Lim,Hyun, AU - Kim,Hyun Pyo, Y1 - 2011/04/06/ PY - 2010/07/29/received PY - 2010/10/04/accepted PY - 2010/09/30/revised PY - 2011/4/7/entrez PY - 2011/4/7/pubmed PY - 2011/7/27/medline SP - 109 EP - 17 JF - Archives of pharmacal research JO - Arch. Pharm. Res. VL - 34 IS - 1 N2 - Matrix metalloproteinase-13 (MMP-13, mammalian collagenase) degrades the cartilage matrix in pathological conditions such as osteoarthritis. Here, to establish the signaling pathway to MMP-13 induction, effects of mitogen-activated protein kinase (MAPK) pathway and the possibility of some other signaling pathways involved are investigated in interleukin-1β (IL-1β)-treated human chondrosarcoma cell line, SW1353 cells. IL-1β (10 ng/mL) treatment induced MMP-13 in SW1353 cells, with concomitant activation of nuclear factor-κB, activator protein-1 (AP-1) and MAPKs, including extracellular signal-regulated protein kinase, p38 MAPK and c-Jun N-terminal kinase. Among these MAPKs, only p38 MAPK inhibitor (SB203580) blocked MMP-13 induction and AP-1 activation in IL-1β-treated SW1353 cells. SB203580 also inhibited c-Fos translocation to the nucleus (but not c-Jun). Importantly, IL-1β treatment induced Janus kinase 2 (JAK2) and signal transducer and activator of transcription 1/2 (STAT1/2) activation. The JAK2 inhibitor (AG490) blocked STAT1/2 activation as well as MMP-13 induction in IL-1β-treated SW1353 cells. STAT1/2 siRNA transfection also reduced MMP-13 expression levels. Thus, from the present study, it is concluded that p38 MAPK/c-Fos/AP-1 and JAK2/STAT1/2 are involved in MMP-13 induction of IL-1β-treated human chondrocytes, SW1353 cells. Blocking these signaling pathways may have chondroprotective effects in cartilage degeneration. SN - 0253-6269 UR - https://www.unboundmedicine.com/medline/citation/21468922/Matrix_metalloproteinase_13_expression_in_IL_1β_treated_chondrocytes_by_activation_of_the_p38_MAPK/c_Fos/AP_1_and_JAK/STAT_pathways_ L2 - https://dx.doi.org/10.1007/s12272-011-0113-4 DB - PRIME DP - Unbound Medicine ER -