کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3105193 1191676 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Changes in the inositol lipid signal system and effects on the secretion of TNF-α by macrophages in severely scalded mice
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی مراقبت های ویژه و مراقبتهای ویژه پزشکی
پیش نمایش صفحه اول مقاله
Changes in the inositol lipid signal system and effects on the secretion of TNF-α by macrophages in severely scalded mice
چکیده انگلیسی

AimIn order to study the mechanism of abnormal macrophage (Mϕ) function in pro-inflammatory cytokine changes after burn, the inositol lipid signal system and its role in tumour necrosis factor-alpha (TNF-α) secretion by peritoneal Mϕs was observed in severely scalded mice.MethodsEighteen percent total body surface area (TBSA) full-thickness scalded mice were used as animal model in this experiment. Peritoneal Mϕs stimulated by lipopolysaccharide in vitro were collected at different time intervals (0, 2, 6, 12, 24 and 48 after burn hour (PBH)), The activities of phosphatidylinositol-phospholipase C (PI-PLC), inositol-1, 4,5, -triphosphate (IP3), protein kinase C (PKC), diacylglycerol (DAG) and TNF-α and the level of Ca2+ concentration in peritoneal Mϕs were measured, and the effects of specific PKC inhibitor H-7 and calmodulin antagonist W-7 on the production of TNF-α were also observed.ResultsAfter scald, increased activities of TNF-α and PLC of Mϕ were observed and peaked at 12 PBH. The activities of DAG and IP3 and the concentration of Ca2+ were markedly increased and reached their peaks at 24 PBH simultaneously. Membrane PKC activity was up-regulated after scald and showed a positive correlation with the change of DAG (r = 0.83, P < 0.05). There was also positive correlation between IP3 and Ca2+ activity (r = 0.946, P < 0.01). When 12 PBH was chosen as the time point for in vitro intervention with the pre-treatment by H-7, both membrane PKC and TNF-α activity decreased significantly. There was no obvious change of TNF-α activity with the application of W-7.ConclusionsThese results indicated that the abnormal activity of TNF-α of Mϕs might be regulated by the inositol lipid signal system following severe burn. The DAG–PKC signal pathway showed closer relationship than IP3-Ca2+ in TNF-α production and could be the optimal target in the prevention and treatment of the systemic inflammatory response syndrome.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Burns - Volume 37, Issue 8, December 2011, Pages 1378–1385
نویسندگان
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