hiv-1 transgene expression in rats induces differential expression of tumor necrosis factor alpha and zinc transporters in the liver and the lunghiv - 1表达的转基因大鼠诱发肿瘤坏死因子α和微分表达式锌转运蛋白在肝脏和肺.pdfVIP

Joshi and Guidot AIDS Research and Therapy 2011, 8:36 /content/8/1/36 RESEARCH Open Access HIV-1 transgene expression in rats induces differential expression of tumor necrosis factor alpha and zinc transporters in the liver and the lung Pratibha C Joshi1,2* and David M Guidot1,2 Abstract Background: Highly effective antiviral treatment can suppress HIV-1 infection, but the chronic effects of HIV-1- related viral proteins, including gp120 and Tat, on organs such as the lungs can be damaging. HIV-1 transgenic rodent models are useful for studying the systemic effects of these proteins independently of viral infection. We have previously shown that HIV-1 transgene expression (and therefore, HIV-1-related protein expression) in rats decreases alveolar macrophage zinc levels and phagocytic capacity by unknown mechanisms. We hypothesized that HIV-1 transgene expression induces chronic inflammation and zinc sequestration within the liver and thereby decreases zinc bioavailability in the lung. We examined the expression of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFa), the zinc storage protein, metallothionein (MT1), and the zinc exporter, ZNT1 in the livers and the lungs of wild type and HIV-1 transgenic rats ± dietary zinc supplementation. In addition, we measured zinc levels, the zinc importing protein ZIP1, and the phagocytic capacity in the alveolar macrophages. Results: HIV-1 transgene expression increased the liver-specific expression of TNFa, suggesting a chronic inflammatory response within the liver in response to HIV-1-related protein expression. In parallel, HIV-1 transgene expression significantly increased MT1 and ZNT1 expression in the liver as compared to the lung, a pattern that is consistent with zinc sequestration in the liver as occurs during systemic inflammation. Further