4.5 Article

PLA2G5 regulates transglutaminase activity of human IL-4-activated M2 macrophages through PGE2 generation

期刊

JOURNAL OF LEUKOCYTE BIOLOGY
卷 100, 期 1, 页码 131-141

出版社

FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.3A0815-372R

关键词

inflammation; eosinophil; nasal polyp; TGM2; phospholipase A(2); asthma

资金

  1. ALA/AAAAI Allergic Respiratory Diseases Award
  2. U.S. National Institutes of Health National Heart, Lung and Blood Institute [R01HL113071, K23HL111113]

向作者/读者索取更多资源

Phospholipases A(2) are enzymes that liberate membrane-bound lipids in a tissue and cell-specific fashion. Group V secretory phospholipase A(2) is necessary for the development of M2 macrophages and their effector functions in a mouse model of the T-helper-2 allergic airway inflammation. However, the function of group V phospholipase A(2) in human M2 activation and T-helper-2 inflammation is ill-defined. Transglutaminase-2, a protein cross-linking enzyme, is a newly identified marker of both human and mouse interleukin-4-activated M2 macrophages and is also found in the lungs of patients with asthma. We report that group V phospholipase A(2) and transglutaminase-2 colocalized in macrophages of human nasal polyp tissue obtained from patients with T-helper-2 eosinophilic inflammation, and their coexpression positively correlated with the number of eosinophils in each tissue specimen. We demonstrate that in human monocyte-derived macrophages activated by interleukin-4, group V phospholipase A(2) translocated and colocalized with transglutaminase-2 in the cytoplasm and on the membrane of macrophages. Moreover, knocking down group V phospholipase A(2) with small interfering ribonucleic acid reduced macrophage transglutaminase activity, whereas mass spectrometry analysis of lipids also showed reduced prostaglandin E-2 production. Finally, exogenous prostaglandin E-2 restored transglutaminase activity of group V phospholipase A(2)-small interfering ribonucleic acid-treated macrophages. Thus, our study shows a novel function of group V phospholipase A(2) in regulating the transglutaminase activity of human interleukin-4-activated M2 macrophages through prostaglandin E-2 generation and suggests that group V phospholipase A(2) is a functionally relevant enzyme that may have therapeutic value for the treatment of human T-helper-2 inflammatory disorders.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据