Endotoxin-induced cytokine and chemokine expression in the HIV-1 transgenic rat
<p>Abstract</p> <p>Background</p> <p>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...
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doaj-f1e79cd39a6848c4ae64be60e0bf35ce2020-11-25T01:01:15ZengBMCJournal of Neuroinflammation1742-20942012-01-0191310.1186/1742-2094-9-3Endotoxin-induced cytokine and chemokine expression in the HIV-1 transgenic ratHomji Natasha FMao XinLangsdorf Erik FChang Sulie L<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p> http://www.jneuroinflammation.com/content/9/1/3HIV-1 transgenic ratendotoxin tolerancecytokineschemokines |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Homji Natasha F Mao Xin Langsdorf Erik F Chang Sulie L |
spellingShingle |
Homji Natasha F Mao Xin Langsdorf Erik F Chang Sulie L Endotoxin-induced cytokine and chemokine expression in the HIV-1 transgenic rat Journal of Neuroinflammation HIV-1 transgenic rat endotoxin tolerance cytokines chemokines |
author_facet |
Homji Natasha F Mao Xin Langsdorf Erik F Chang Sulie L |
author_sort |
Homji Natasha F |
title |
Endotoxin-induced cytokine and chemokine expression in the HIV-1 transgenic rat |
title_short |
Endotoxin-induced cytokine and chemokine expression in the HIV-1 transgenic rat |
title_full |
Endotoxin-induced cytokine and chemokine expression in the HIV-1 transgenic rat |
title_fullStr |
Endotoxin-induced cytokine and chemokine expression in the HIV-1 transgenic rat |
title_full_unstemmed |
Endotoxin-induced cytokine and chemokine expression in the HIV-1 transgenic rat |
title_sort |
endotoxin-induced cytokine and chemokine expression in the hiv-1 transgenic rat |
publisher |
BMC |
series |
Journal of Neuroinflammation |
issn |
1742-2094 |
publishDate |
2012-01-01 |
description |
<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p> |
topic |
HIV-1 transgenic rat endotoxin tolerance cytokines chemokines |
url |
http://www.jneuroinflammation.com/content/9/1/3 |
work_keys_str_mv |
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