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Alcohol Suppresses IL‐2–Induced CC Chemokine Production by Natural Killer Cells
Author(s) -
Zhang Ting,
Guo ChangJiang,
Douglas Steven D.,
Metzger David S.,
O’Brien Charles P.,
Li Yuan,
Wang YanJian,
Wang Xu,
Ho WenZhe
Publication year - 2005
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000179364.32003.9f
Subject(s) - chemokine , ccl5 , biology , chemokine receptor ccr5 , interleukin 12 , cc chemokine receptors , cxcl16 , interleukin 21 , chemokine receptor , lymphokine activated killer cell , innate immune system , microbiology and biotechnology , chemistry , immune system , immunology , t cell , cytotoxic t cell , il 2 receptor , in vitro , biochemistry
Background: Natural killer (NK) cells are a critical component of the host innate immune system. We investigated whether alcohol impairs NK cell function, particularly production of CC chemokines induced by interleukin (IL)‐2, the natural ligands for CCR5 receptor. Methods: Primary NK cells and NK cell line (YTS) were cultured with or without alcohol (10 to 80 mM) for three hours. The culture supernatants were then harvested and used to treat human peripheral blood monocyte‐derived macrophages and a HeLa cell line, which expresses CD4, CCR5, and CXCR4 receptors (MAGI cells). CC chemokine expression by YTS and primary NK cells treated with or without alcohol was analyzed with the real‐time RT‐PCR and ELISA. Ca 2+ i and Western blot assays were used to determine calcium‐mediated intracellular signaling pathway and NF‐κB p65 expression. HIV strains (Bal and UG024) were used to infect macrophages and MAGI cells. In addition, ADA (macrophage‐tropic strain) and murine leukemia virus (MLV) envelope‐pseudotyped HIV infection was carried out in macrophages. HIV infectivity was determined by HIV reverse transcriptase (RT) and β‐galactosidase activity assays. Results: Alcohol inhibited IL‐2–induced CC chemokine (CCL3 and CCL4) expression by NK cells. Functional tests demonstrated that this reduced expression of CC chemokines was associated with diminished anti‐HIV ability of NK cells. Alcohol also reduced the ability of NK cells to response to CCL3‐mediated chemotaxis. Alcohol inhibited IL‐2–induced NF‐κB p65 protein expression and calcium mobilization by NK cells. Conclusions: Alcohol, through the inhibition of IL‐2–induced NF‐κB p65 protein expression and intracellular calcium mobilization, suppressed NK cell production of CC chemokines. This suppression of CC chemokine production was associated with diminished anti‐HIV activity of NK cells. Thus, by inhibiting NK cell–mediated innate immunity against HIV, alcohol consumption may have a cofactor role in the immunopathogenesis of HIV disease.