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Differential down-regulation of COX-2 and MMP-13 in human skin fibroblasts by glucosamine-hydrochloride.

Abstract：

BACKGROUND:Evidence suggests anti-inflammatory effects of glucosamine (GS) on inflammatory diseases. COX-2 is an enzyme to produce prostaglandins. MMPs are the family of matrix metalloproteinases degradable of ECM. Excess expression of COX-2 or MMPs involves in skin inflammation. OBJECTIVE:We evaluated whether GS-HCl modulates expression of COX-2 and/or MMPs by IL-1beta or PMA in human skin fibroblasts (HSF) or keratinocytes (HaCaT). METHODS:HSF or HaCaT cells were exposed to IL-1beta or PMA without or with GS-HCl. COX-2 or MMPs protein and mRNA expression, respectively, were analyzed by Western blot and RT-PCR. MTS assay was utilized to assess the cytotoxicity of GS-HCl on HSF cells. RESULTS:In HSF cells, IL-1beta treatment induced COX-2 and MMP-13 expressions in association with activation of ERKs, p38 MAPK, JNKs, and NF-kappaB. PMA treatment also induced COX-2 and MMP-13 expressions in association with p38 MAPK activation. Of interest, treatment with GS-HCl (10mM) led to blockage of p38 MAPK activation, accumulation of 66kDa COX-2 protein variant (without affecting COX-2 mRNA expression), and transcriptional down-regulation of MMP-13 in the IL-1beta- or PMA-treated HSF cells. Distinctly, pharmacological inhibition of p38 MAPK with SB203580 was associated with transcriptional down-regulation of COX-2 and MMP-13 in the IL-1beta- or PMA-treated HSF cells. In addition, the GS-HCl-mediated COX-2 protein modification was observed in both endogenous and PMA-induced COX-2 in HaCaT cells. CONCLUSIONS:GS-HCl differentially down-regulates COX-2 and MMP-13 expression in the IL-1beta- or PMA-treated human skin fibroblasts via the p38 MAPK-independent COX-2 translational inhibition and the p38 MAPK-dependent MMP-13 transcriptional suppression, respectively.

journal_name

J Dermatol Sci

journal_title

Journal of dermatological science

authors

Hong H,Park YK,Choi MS,Ryu NH,Song DK,Suh SI,Nam KY,Park GY,Jang BC

doi

10.1016/j.jdermsci.2009.06.017

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

43-50

issue

1

eissn

0923-1811

issn

1873-569X

pii

S0923-1811(09)00198-4

journal_volume

56

pub_type

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