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调节妊娠非肥胖型糖尿病(NOD)小鼠巨噬细胞炎症表型。

Modulation of macrophage inflammatory profile in pregnant nonobese diabetic (NOD) mice.

机构信息

Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.

出版信息

Mol Cell Endocrinol. 2011 Feb 20;333(2):112-8. doi: 10.1016/j.mce.2010.11.035. Epub 2010 Dec 8.

Abstract

During normal early pregnancy circulating monocytes are recruited to the maternal-placental interface where they differentiate to macrophages expressing different functional phenotypes for the maintenance of tissue homeostasis. Pregnancy in the nonobese diabetic (NOD) mouse model presents some pathological features in the pre-diabetic stage. The aim of this work was to analyze the functional profile of peritoneal macrophages faced with inflammatory and phagocytic stimuli in early pregnant pre-diabetic NOD mice and their modulation by vasoactive intestinal peptide (VIP). Pregnant NOD mouse macrophages showed no basal NFκB activation, lower IL-12 and nitrites production compared with the macrophages from non-pregnant NOD mice. Their pro-inflammatory aberrant response to LPS and apoptotic cell challenge was reduced and VIP inhibited macrophage residual deleterious responses to apoptotic cells. A functional phenotype switch in macrophages during pregnancy in NOD mice and a promoting effect of VIP towards this regulatory phenotype would be in line with the central role of macrophages in the maternal-placental dialogue.

摘要

在正常的早孕期间,循环单核细胞被招募到母胎界面,在那里它们分化为表达不同功能表型的巨噬细胞,以维持组织内稳态。非肥胖型糖尿病(NOD)小鼠模型中的妊娠在糖尿病前期阶段呈现出一些病理特征。本研究的目的是分析在早期妊娠糖尿病前期 NOD 小鼠中面对炎症和吞噬刺激时腹膜巨噬细胞的功能特征,以及血管活性肠肽(VIP)对其的调节作用。与非妊娠 NOD 小鼠的巨噬细胞相比,怀孕 NOD 小鼠的巨噬细胞没有基础 NFκB 激活,产生的 IL-12 和亚硝酸盐较少。它们对 LPS 和凋亡细胞挑战的异常促炎反应减少,而 VIP 抑制了巨噬细胞对凋亡细胞的残余有害反应。NOD 小鼠妊娠期间巨噬细胞的功能表型转换以及 VIP 对这种调节表型的促进作用,与巨噬细胞在母胎对话中的核心作用一致。

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