Role of CLIC4 in the host innate responses to bacterial lipopolysaccharide

Guoan He, Yao Ma, Szu Yi Chou, Huihong Li, Chingwen Yang, Jen Zen Chuang, Ching Hwa Sung, Aihao Ding

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Chloride intracellular channel (CLIC) 4 has diverse functions in membrane trafficking, apoptosis, angiogenesis and cell differentiation. CLIC4 is abundantly expressed in macrophages, but its role in innate immune functions is unclear. 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-6, IL-12 and CCL5 than mock transfectants when exposed to LPS. To explore the role of CLIC4 in vivo, we generated CLIC4-null mice. These mice were protected from LPS-induced death, and had reduced serum levels of inflammatory cytokines. Upon infection with Listeria monocytogenes, CLIC4-deficient mice were impaired in their ability to clear infection, and their macrophages responded to Listeria by producing less inflammatory cytokines and chemokines than the WT controls. When challenged with LPS in vitro, deletion of clic4 gene had little effect on MAPK and NF-κB activation, but led to a reduced accumulation of phosphorylated interferon response factor 3 (IRF3) within macrophages. Conversely, overexpression of CLIC4 enhanced LPS-mediated IRF3. Thus, these findings suggest that CLIC4 is an LPS-induced product that can serve as a positive regulator of LPS signaling.

Original languageEnglish
Pages (from-to)1221-1230
Number of pages10
JournalEuropean Journal of Immunology
Volume41
Issue number5
DOIs
Publication statusPublished - May 2011

Keywords

  • Inflammation
  • Innate responses
  • Macrophage
  • TLR-signaling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Role of CLIC4 in the host innate responses to bacterial lipopolysaccharide'. Together they form a unique fingerprint.

Cite this