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Here, we show that primary murine macrophages express increased amounts of CLIC4 after exposure to bacterial lipopolysaccharide (LPS). Endogenous CLIC4 level was significantly elevated in the brain, heart, lung, kidney, liver and spleen after LPS injection of mice. Stable macrophage lines overexpressing CLIC4 produced more TNF, IL\u20106, IL\u201012 and CCL5 than mock transfectants when exposed to LPS. To explore the role of CLIC4 in vivo, we generated CLIC4\u2010null mice. These mice were protected from LPS\u2010induced death, and had reduced serum levels of inflammatory cytokines. Upon infection with <jats:italic>Listeria monocytogenes<\/jats:italic>, CLIC4\u2010deficient mice were impaired in their ability to clear infection, and their macrophages responded to <jats:italic>Listeria<\/jats:italic> by producing less inflammatory cytokines and chemokines than the WT controls. When challenged with LPS in vitro, deletion of <jats:italic>clic4<\/jats:italic> gene had little effect on MAPK and NF\u2010\u03baB activation, but led to a reduced accumulation of phosphorylated interferon response factor 3 (IRF3) within macrophages. Conversely, overexpression of CLIC4 enhanced LPS\u2010mediated IRF3. Thus, these findings suggest that CLIC4 is an LPS\u2010induced product that can serve as a positive regulator of LPS signaling.<\/jats:p>","DOI":"10.1002\/eji.201041266","type":"journal-article","created":{"date-parts":[[2011,2,26]],"date-time":"2011-02-26T14:48:31Z","timestamp":1298731711000},"page":"1221-1230","source":"Crossref","is-referenced-by-count":51,"title":["Role of CLIC4 in the host innate responses to bacterial lipopolysaccharide"],"prefix":"10.1002","volume":"41","author":[{"given":"Guoan","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szu\u2010Yi","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chingwen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen\u2010Zen","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Hwa","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihao","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,4,20]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1087-0024.2005.200402.x"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007874200"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107804200"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20324"},{"key":"e_1_2_6_6_2","first-page":"F398","article-title":"A novel p64\u2010related Cl\u2010 channel: subcellular distribution and nephron segment\u2010specific expression","volume":"276","author":"Edwards J. 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