Article

Endotoxin-induced cytokine and chemokine expression in the HIV-1 transgenic rat

Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ 07079, USA.
Journal of Neuroinflammation (Impact Factor: 5.41). 01/2012; 9(1):3. DOI: 10.1186/1742-2094-9-3
Source: PubMed

ABSTRACT

Repeated exposure to a low dose of a bacterial endotoxin such as lipopolysaccharide (LPS) causes immune cells to become refractory to a subsequent endotoxin challenge, a phenomenon known as endotoxin tolerance (ET). During ET, there is an imbalance in pro- and anti-inflammatory cytokine and chemokine production, leading to a dysregulated immune response. HIV-1 viral proteins are known to have an adverse effect on the immune system. However, the effects of HIV-1 viral proteins during ET have not been investigated.
In this study, HIV-1 transgenic (HIV-1Tg) rats and control F344 rats (n = 12 ea) were randomly treated with 2 non-pyrogenic doses of LPS (LL) to induce ET, or saline (SS), followed by a high challenge dose of LPS (LL+L, SS+L) or saline (LL+S, SS+S). The gene expression of 84 cytokines, chemokines, and their receptors in the brain and spleen was examined by relative quantitative PCR using a PCR array, and protein levels in the brain, spleen, and serum of 7 of these 84 genes was determined using an electrochemiluminescent assay.
In the spleen, there was an increase in key pro-inflammatory (IL1α, IL-1β, IFN-γ) and anti-inflammatory (IL-10) cytokines, and inflammatory chemokines (Ccl2, Ccl7, and Ccl9,) in response to LPS in the SS+L and LL+L (ET) groups of both the HIV-1Tg and F344 rats, but was greater in the HIV-1Tg rats than in the F344. In the ET HIV-1Tg and F344 (LL+L) rats in the spleen, the LPS-induced increase in pro-inflammatory cytokines was diminished and that of the anti-inflammatory cytokine was enhanced compared to the SS+L group rats. In the brain, IL-1β, as well as the Ccl2, Ccl3, and Ccl7 chemokines were increased to a greater extent in the HIV-1Tg rats compared to the F344; whereas Cxcl1, Cxcl10, and Cxcl11 were increased to a greater extent in the F344 rats compared to the HIV-1Tg rats in the LL+L and SS+L groups.
Our data indicate that the continuous presence of HIV-1 viral proteins can have tissue-dependent effects on endotoxin-induced cytokine and chemokine expression in the ET state.

Download full-text

Full-text

Available from: Natasha F Homji
  • Source
    • "Collectively, these findings indicate that LPS enhances the sensitivity of morphineinduced CPP and that an inflammatory response that occurs during morphine use may result in more extensive behavioral changes than previously thought. There is an imbalance between proinflammatory and anti-inflammatory cytokines during endotoxin tolerance, and the immune cells become desensitized to an additional endotoxin challenge [12]. In this study, an endotoxin tolerance effect was observed in the group of rats pretreated with low dose LPS (LL). "

    Preview · Article · Jan 2016
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prior exposure of innate immune cells to lipopolysaccharide (LPS) has caused them to be refractory to further endotoxin stimulation, also termed endotoxin tolerance (ET). Bacterial LPS signals through Toll-like receptor (TLR) 4, which was thought to enable the innate immune system to deal with invasive pathogens and to restrain systemic inflammation efficiently. We established a robust model of ET and determined the level of TNF-α and IL-6 in cultured human monocytes. Then, microarray assay was applied to assess gene expression in this model. The results showed that 356 non-tolerizable genes were differentially expressed at a high level in tolerant monocytes. The genes selected were classified into several categories based on gene ontology (GO) and KEGG pathway database. And then literature annotations, protein-protein interaction (PPI) network, and functional consistency were applied to analyze the non-tolerizable genes. Finally, the microarray results were verified by quantitative real-time PCR of seven representative genes, including the two candidate genes, Spry2 and Smurf2, which were supposed to play a critical role in TLRs-induced inflammation based on literature retrieval. Our results would provide useful information for further analysis of regulating TLRs-induced inflammation, and would facilitate the study of associated mechanisms.
    No preview · Article · Jul 2012 · Inflammation
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Morphine is widely used for its analgesic effects. In addition to its high potential for addiction and tolerance, morphine also induces immunosuppression. Inflammasomes, NLRP3 being the most characterized, is a platform for activation of pro-inflammatory cytokines, particularly IL-1β. We have explored the effects of lipopolysaccharide (LPS) during morphine tolerance on expression of the NLRP3 inflammasome and related inflammatory genes. Methods: Morphine-pellet administration was used to induce morphine tolerance in F344 rats. Control rats were given a placebo. On day 5, the animals received either saline or 250 μg/kg LPS. LPS-induced protein expression of TNF-α, IL-1β, and IL- 6 was examined in the spleen of rats with and without morphine tolerance. A PCR array was used to examine LPS-induced expression of 84 inflammasome-related genes with and without morphine tolerance. Results: LPS-induced IL-1β and TNF-α protein expression was significantly lower in the spleen of the morphine-tolerant animals than in the placebo-control animals. In response to LPS, expression of 27 genes, including NLRP3, TNF-α, IL-1β, and IL-6, was significantly increased, and expression of 3 genes was significantly decreased in both the morphine-tolerant and placebo-control groups compared to the saline-treated animals. However, there was only a 2.7-fold increase in NLRP3 expression in response to LPS in the morphine-tolerant rats compared to a 4.5-fold increase in the placebo-control animals. Conclusion: Our data indicate that, in the morphine-tolerant state, LPS-induced expression of NLRP3 is suppressed and cytokine/chemokine expression is inhibited, which may be one of the mechanisms involved in morphine-induced immunosuppression.
    No preview · Article · Jan 2013 · Drug and alcohol dependence
Show more

Similar Publications