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Arsenic trioxide regulates the production and activities of matrix metalloproteinases-1, -2, and -9 in fibroblasts and THP-1 / 中华医学杂志(英文版)
Chinese Medical Journal ; (24): 4481-4487, 2012.
Article in English | WPRIM | ID: wpr-331349
ABSTRACT
<p><b>BACKGROUND</b>The elevated matrix metalloproteinase (MMP) activity is an important cause of chronic wound healing failure. Arsenolite, whose main component is arsenic trioxide (As2O3), is a common traditional Chinese medicine wildly used in treating chronic wounds; it can remove necrotic tissue and promote tissue regeneration. This research was designed to evaluate the effects of As2O3 on production and activities of MMP-1, MMP-2 and MMP-9, and on regulation of its signal transduction pathway in human skin fibroblasts (HSFb) and human monocyte line (THP-1 cells) that were in an inflammatory state.</p><p><b>METHODS</b>We established three cell models; HSFb activated by TNF-α, THP-1 cells activated by phorbol 12-myristate 13-acetate (PMA) and an HSFb-THP-1 co-culture system. Three cell models was cultured with As2O3 for 24 hours. The levels of MMP-1, MMP-2, MMP-9, TNF-α and IL-1β in the cell culture supernatants were assayed by ELISA. The mRNA expressions of MMP-1, MMP-2 and MMP-9 were determined by RT-PCR. The activities of MMP-2 and MMP-9 were tested by Gelatin zymography assays. The phosphorylation levels of ERK1/2 and p38MAPK were assayed by Western blotting.</p><p><b>RESULTS</b>As2O3 inhibited the expression of MMP-1, MMP-2 and MMP-9 mRNA, the secretion and activity of MMP-1, MMP-2 and MMP-9 in HSFb and THP-1 cells in the inflammatory state (P < 0.05 and P < 0.01 respectively). It also inhibited the secretion of TNF-α and IL-1β in THP-1 cells and in the co-culture system (P < 0.05 and P < 0.01, respectively). It also decreased the phosphorylation of ERK1/2 and p38 MAPK in HSFb and THP-1 cells (P < 0.05 and P < 0.01, respectively).</p><p><b>CONCLUSIONS</b>As2O3, as a main component of arsenolite, can inhibit the production of MMPs by HSFb and THP-1 cells in an inflammatory state through inhibiting the release of inflammatory factors and the activation of the MAPK cascade pathway. This may be a possible mechanism for arsenolite healing chronic wounds.</p>
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Oxides / Pharmacology / Arsenicals / Monocytes / Cell Line / Cells, Cultured / Interleukin-1 / Tumor Necrosis Factor-alpha / Matrix Metalloproteinase 2 / Matrix Metalloproteinase 9 Type of study: Prognostic study Limits: Humans Language: English Journal: Chinese Medical Journal Year: 2012 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Oxides / Pharmacology / Arsenicals / Monocytes / Cell Line / Cells, Cultured / Interleukin-1 / Tumor Necrosis Factor-alpha / Matrix Metalloproteinase 2 / Matrix Metalloproteinase 9 Type of study: Prognostic study Limits: Humans Language: English Journal: Chinese Medical Journal Year: 2012 Type: Article