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Báo cáo y học: "Suppression of LPS-induced matrixmetalloproteinase responses in macrophages exposed to phenytoin and its metabolite, 5-(p-hydroxyphenyl-), 5-phenylhydantoin"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Suppression of LPS-induced matrixmetalloproteinase responses in macrophages exposed to phenytoin and its metabolite, 5-(p-hydroxyphenyl-), 5-phenylhydantoin. | Serra et al. Journal of Inflammation 2010 7 48 http www.journal-inflammation.eom content 7 1 48 JOURNAL OF INFLAMMATION RESEARCH Open Access Suppression of LPS-induced matrixmetalloproteinase responses in macrophages exposed to phenytoin and its metabolite 5- p-hydroxyphenyl- 5-phenylhydantoin 1 1 2 1 Ryan Serra Abdel-ghany Al-saidi Nikola Angelov Salvador Nares Abstract Background Phenytoin PHT has been reported to induce gingival gum overgrowth GO in approximately 50 of patients taking this medication. While most studies have focused on the effects of PHT on the fibroblast in the pathophysiology underlying GO few studies have investigated the potential regulatory role of macrophages in extracellular matrix ECM turnover and secretion of proinflammatory mediators. The aim of this study was to evaluate the effects of PHT and its metabolite 5- p-hydroxyphenyl- 5-phenylhydantoin HPPH on LPS-elicited MMP TIMP TNF-a and IL-6 levels in macrophages. Methods Human primary monocyte-derived macrophages n 6 independent donors were pretreated with 1550 gg mL PHT-Na or 15-50 gg mL HPPH for 1 hour. Cells were then challenged with 100 ng ml purified LPS from the periodontal pathogen Aggregatibacter actinomycetemcomitans. Supernatants were collected after 24 hours and levels of MMP-1 MMP-2 MMP-3 MMP-9 MMP-12 TIMP-1 TIMP-2 TIMP-3 TIMP-4 TNF-a and IL-6 determined by multiplex analysis or enzyme-linked immunoadsorbent assay. Results A dose-dependent inhibition of MMP-1 MMP-3 MMP-9 TIMP-1 but not MMP-2 was noted in culture supernatants pretreated with PHT or HPPH prior to LPS challenge. MMP-12 TIMP-2 TIMP-3 and TIMP-2 were not detected in culture supernatants. High concentrations of PHT but not HPPH blunted LPS-induced TNF-a production although neither significantly affected IL-6 levels. Conclusion The ability of macrophages to mediate turnover of ECM via the production of metalloproteinases is compromised not only by PHT but its metabolite HPPH in a dose-dependent fashion. Further .