Guggulsterone blocks IL-1beta-mediated inflammatory responses by suppressing NF-kappaB activation in fibroblast-like synoviocytes.
Guggulsterone is a plant sterol that is used to treat hyperlipidemia, arthritis, and obesity. Although its anti-inflammatory and anti-hyperlipidemic effects have been well documented, the effect of guggulsterone on fibroblast-like synoviocytes (FLS) has not yet been reported. Therefore, in this study, the effect of guggulsterone on interleukin (IL)-1beta-induced inflammatory responses in the FLS of rheumatic patients was investigated. Treatment of FLS with IL-1beta induced production of chemokines such as RANTES and ENA-78. In addition, Western blot analysis and gelatin zymography revealed that IL-1beta activated matrix metalloproteinase (MMP)-1 and -3 in FLS. However, pre-incubation with guggulsterone completely inhibited the ability of IL-1beta to induce the production of chemokines and to activate MMPs. Although the NF-kappaB binding activity and nuclear p50 and p65 subunit levels, as well as IkappaBalpha degradation in the cytoplasm was greater in cells stimulated with IL-1beta than in unstimulated cells, treatment with guggulsterone abolished all of these increases. Collectively, these results suggest that guggulsterone would be useful as an inhibitor of joint destruction in patients with rheumatoid arthritis.
Lee
Young-Rae
YR
Department of Biochemistry, Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk, 561-756, Republic of Korea.
Lee
Ji-Hyun
JH
Noh
Eun-Mi
EM
Kim
Eun-Kyung
EK
Song
Mi-Young
MY
Jung
Won-Seok
WS
Park
Sung-Joo
SJ
Kim
Jong-Suk
JS
Park
Jin-Woo
JW
Kwon
Kang-Beom
KB
Park
Byung-Hyun
BH
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011282:Pregnenediones / Q000494:pharmacology*; D013583:Synovial Membrane / Q000166:cytology / Q000201:enzymology / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D016328:NF-kappa B; D011282:Pregnenediones; C023617:pregna-4,17-diene-3,16-dione; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1