Channelpedia

PubMed 22474389


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClIC4 , Slo1



Title: Inducible NOS-induced chloride intracellular channel 4 (CLIC4) nuclear translocation regulates macrophage deactivation.

Authors: Mariam Malik, Kasey Jividen, V C Padmakumar, Christophe Cataisson, Luowei Li, Jessica Lee, O M Zack Howard, Stuart H Yuspa

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2012 Apr 17 , 109, 6130-5

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22474389


Abstract
Nuclear translocation of cytosolic CLIC4 is an essential feature of its proapoptotic and prodifferentiation functions. Here we demonstrate that CLIC4 is induced concurrently with inducible nitric oxide synthase (iNOS) and S-nitrosylated in proinflammatory peritoneal macrophages. Chemical inhibition or genetic ablation of iNOS inhibits S-nitrosylation and nuclear translocation of CLIC4. In macrophages, iNOS-induced nuclear CLIC4 coincides with the pro- to anti-inflammatory transition of the cells because IL-1β and CXCL1 mRNA remain elevated in CLIC4 and iNOS knockout macrophages at late time points, whereas TNFα mRNA is elevated only in the iNOS knockout macrophages. Active IL-1β remains elevated in CLIC4 knockout macrophages and in macrophages in which CLIC4 nuclear translocation is prevented by the NOS inhibitor l-NAME. Moreover, overexpression of nuclear-targeted CLIC4 down-regulates IL-1β in stimulated macrophages. In mice, genetically null for CLIC4, the number of phagocytosing macrophages stimulated by LPS is reduced. Thus, iNOS-induced nuclear CLIC4 is an essential part of the macrophage deactivation program.