کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2515473 1118525 2007 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The anti-inflammatory actions of LCY-2-CHO, a carbazole analogue, in vascular smooth muscle cells
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
The anti-inflammatory actions of LCY-2-CHO, a carbazole analogue, in vascular smooth muscle cells
چکیده انگلیسی

LCY-2-CHO has anti-inflammatory actions on macrophages. To understand its therapeutic implication in atherosclerosis, we examined its effects on the expressions of anti-inflammatory and inflammatory proteins in cultured rat aortic vascular smooth muscle cells (VSMC). LCY-2-CHO is able to induce heme oxygenase-1 (HO-1) protein expression through a transcriptional action. The HO-1 inducting effect of LCY-2-CHO was inhibited by SB203580, NG-nitro-l-arginine methylester (l-NAME), and wortmannin, but was not affected by U0126 or SP600125. In accordance LCY-2-CHO increased protein phosphorylation of p38, Akt, and eNOS. Nrf2 is a transcription factor essential for HO-1 gene induction and we showed that LCY-2-CHO is able to cause Nrf2 nuclear translocation and this action depends on p38, Akt and eNOS. In addition to induce anti-inflammatory HO-1, LCY-2-CHO reduced interleukin-1β (IL-1β)-induced inflammatory mediators, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), growth-related oncogene protein-alpha (GRO-α), and interleukin-8 (IL-8). Inhibitory effect on IL-1β-mediated NF-κB activation was evidenced by the diminishment of IκB kinase (IKK) phosphorylation and IκBα degradation. In contrast, IL-1β-mediated ERK and JNK activations were not changed by LCY-2-CHO, while p38 activation by IL-1β and LCY-2-CHO displayed the non-additivity. Taken together, given the overall anti-inflammatory properties of LCY-2-CHO in VSMC, in terms to induce HO-1 gene expression and inhibit inflammatory gene expression, these results highlight the therapeutic potential of LCY-2-CHO in atherosclerosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 74, Issue 2, 15 July 2007, Pages 298–308
نویسندگان
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