Taurine chloramine differentially inhibits matrix metalloproteinase 1 and 13 synthesis in interleukin-1beta stimulated fibroblast-like synoviocytes.
It has been suggested that taurine chloramine (TauCl) plays an important role in the downregulation of proinflammatory mediators. However, little is known about its effect on the expression of matrix metalloproteinases (MMPs). In this study, we investigated the effects of TauCl on synovial expression of MMPs. The effects of TauCl on MMP expression in IL-1beta stimulated fibroblast-like synoviocytes (FLSs) were studied using the following techniques. Real-time PCR and semi-quantitative PCR were employed to analyze the mRNA expression of MMPs. ELISA was used to determine protein levels of MMPs. Western blot analyses were performed to analyze the mitogen-activated protein kinase and inhibitor of nuclear factor-kappaB (IkappaB) kinase signalling pathways. Finally, electrophoretic mobility shift assay and immunohistochemistry were used to assess localization of transcription factors. IL-1beta increased the transcriptional and translational levels of MMP-1 and MMP-13 in rheumatoid arthritis FLSs, whereas the levels of MMP-2 and MMP-9 were unaffected. TauCl at a concentration of 400 to 600 micromol/l greatly inhibited the transcriptional and translational expression of MMP-13, but the expression of MMP-1 was significantly inhibited at 800 micromol/l. At a concentration of 600 micromol/l, TauCl did not significantly inhibit phosphorylation of mitogen-activated protein kinase or IkappaB degradation in IL-1beta stimulated rheumatoid arthritis FLSs. The degradation of IkappaB was significantly inhibited at a TauCl concentration of 800 micromol/l. The inhibitory effect of TauCl on IkappaB degradation was confirmed by electrophoretic mobility shift assay and immunochemical staining for localization of nuclear factor-kappaB. TauCl differentially inhibits the expression of MMP-1 and MMP-13, and inhibits expression of MMP-1 primarily through the inhibition of IkappaB degradation, whereas it inhibits expression of MMP-13 through signalling pathways other than the IkappaB pathway.
Kim
Kyoung Soo
KS
East-West Bone & Joint Research Center, East-West Neo Medical Center, Kyung Hee University, Sangil-dong, Gangdong-gu, Seoul, Republic of Korea. labrea46@yahoo.co.kr
Park
Eun Kyung
EK
Ju
Seung Min
SM
Jung
Hye-Sook
HS
Bang
Jun Soo
JS
Kim
Chaekyun
C
Lee
Yeon-Ah
YA
Hong
Seung-Jae
SJ
Lee
Sang-Hoon
SH
Yang
Hyung-In
HI
Yoo
Myung Chul
MC
D001172:Arthritis, Rheumatoid; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D015398:Signal Transduction; D013583:Synovial Membrane / Q000166:cytology; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D061965:Matrix Metalloproteinase Inhibitors; D013654:Taurine; C043410:N-chlorotaurine; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1
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