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Effects of pristane alone or combined with chloroquine on macrophage activation, oxidative stress, and TH1/TH2 skewness.

Ouyang Q, Huang Z, Wang Z, Chen X, Ni J, Lin L - J Immunol Res (2014)

Bottom Line: And the expression of T-bet/GATA-3 and IL-12/IL-10 mRNA in spleen were analyzed by real-time PCR.In parallel, a significant increase in lipid peroxidation and a decrease in superoxide dismutase, glutathione, and catalase activity, as well as a skewed Th1/Th2 balance in spleen, were observed.However, chloroquine supplementation showed a remarkable amelioration of these abnormalities.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road 34, Quanzhou, Fujian 362000, China.

ABSTRACT
We investigated the protective role of chloroquine against pristane-induced macrophage activation, oxidative stress, and Th1/Th2 skewness in C57BL/6J mice. Those mice were treated with pristane alone or combined with chloroquine. Hematological and biochemical parameters, macrophage phagocytic function, the oxidant/antioxidant index, cytokine for IFN-γ, TNF-α, IL-4, and IL-6, and the isotypes of IgG2a and IgG1 were determined. And the expression of T-bet/GATA-3 and IL-12/IL-10 mRNA in spleen were analyzed by real-time PCR. We found that pristane treatment for a period of 12 or 24 weeks triggered macrophage activation syndrome, characterized by hemophagocytosis in spleen and peripheral blood, enhanced lipid phagocytosis by peritoneal macrophages in vitro, erythropenia and leucopenia, increased anti-Smith, lactic dehydrogenase, triglyceride, and ferritin, as well as hypercytokinemia of IFN-γ, TNF-α, IL-4, and IL-6. In parallel, a significant increase in lipid peroxidation and a decrease in superoxide dismutase, glutathione, and catalase activity, as well as a skewed Th1/Th2 balance in spleen, were observed. However, chloroquine supplementation showed a remarkable amelioration of these abnormalities. Our data indicate that pristane administration induces macrophage activation, oxidative stress, and Th1/Th2 skewness, which can be attenuated by chloroquine.

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Effects of pristane alone or in combination with chloroquine on Th1/Th2 associated gene expression by RT-PCR analysis. Relative mRNA expression was normalized to GAPDH. CQ: chloroquine. Bars represent mean ± SE of three replicate experiments, *P < 0.05 versus the corresponding control mice, #P < 0.05 versus mice exposure to pristane for 12 weeks.
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fig5: Effects of pristane alone or in combination with chloroquine on Th1/Th2 associated gene expression by RT-PCR analysis. Relative mRNA expression was normalized to GAPDH. CQ: chloroquine. Bars represent mean ± SE of three replicate experiments, *P < 0.05 versus the corresponding control mice, #P < 0.05 versus mice exposure to pristane for 12 weeks.

Mentions: Considering that Th1 cells have a central role in macrophage activation, we next quantified the expression of Th1- (T-bet, IL-12p35) and Th2-related genes (GATA-3, IL-4) in spleen. At 12 weeks after injection, Th1-associated genes (T-bet, IL-12) were strikingly upregulated by 73.2-fold, 49.7-fold, respectively. While GATA-3 altered insignificantly, IL-4 rose moderately. The ratios of T-bet/GATA-3 and IL-12/IL-10 were 11.91 and 8.11, respectively. At 24 weeks after pristane injection, Th1-dependent gene further increased and paralleled the elevated Th2-related genes. Conversely, the levels of T-bet, IL-12p35, and IL-4 mRNA were decreased following coadministration of CQ and pristane for 12 weeks. Collectively, these data suggested that pristane induced a Th1-biased response at 12 weeks, while it induced a mixed Th1/Th2 gene phenotype at 24 weeks after injection. CQ treatment attenuated the pristane-induced Th1-biased immune response (Figure 5).


Effects of pristane alone or combined with chloroquine on macrophage activation, oxidative stress, and TH1/TH2 skewness.

Ouyang Q, Huang Z, Wang Z, Chen X, Ni J, Lin L - J Immunol Res (2014)

Effects of pristane alone or in combination with chloroquine on Th1/Th2 associated gene expression by RT-PCR analysis. Relative mRNA expression was normalized to GAPDH. CQ: chloroquine. Bars represent mean ± SE of three replicate experiments, *P < 0.05 versus the corresponding control mice, #P < 0.05 versus mice exposure to pristane for 12 weeks.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4127244&req=5

fig5: Effects of pristane alone or in combination with chloroquine on Th1/Th2 associated gene expression by RT-PCR analysis. Relative mRNA expression was normalized to GAPDH. CQ: chloroquine. Bars represent mean ± SE of three replicate experiments, *P < 0.05 versus the corresponding control mice, #P < 0.05 versus mice exposure to pristane for 12 weeks.
Mentions: Considering that Th1 cells have a central role in macrophage activation, we next quantified the expression of Th1- (T-bet, IL-12p35) and Th2-related genes (GATA-3, IL-4) in spleen. At 12 weeks after injection, Th1-associated genes (T-bet, IL-12) were strikingly upregulated by 73.2-fold, 49.7-fold, respectively. While GATA-3 altered insignificantly, IL-4 rose moderately. The ratios of T-bet/GATA-3 and IL-12/IL-10 were 11.91 and 8.11, respectively. At 24 weeks after pristane injection, Th1-dependent gene further increased and paralleled the elevated Th2-related genes. Conversely, the levels of T-bet, IL-12p35, and IL-4 mRNA were decreased following coadministration of CQ and pristane for 12 weeks. Collectively, these data suggested that pristane induced a Th1-biased response at 12 weeks, while it induced a mixed Th1/Th2 gene phenotype at 24 weeks after injection. CQ treatment attenuated the pristane-induced Th1-biased immune response (Figure 5).

Bottom Line: And the expression of T-bet/GATA-3 and IL-12/IL-10 mRNA in spleen were analyzed by real-time PCR.In parallel, a significant increase in lipid peroxidation and a decrease in superoxide dismutase, glutathione, and catalase activity, as well as a skewed Th1/Th2 balance in spleen, were observed.However, chloroquine supplementation showed a remarkable amelioration of these abnormalities.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Zhongshan North Road 34, Quanzhou, Fujian 362000, China.

ABSTRACT
We investigated the protective role of chloroquine against pristane-induced macrophage activation, oxidative stress, and Th1/Th2 skewness in C57BL/6J mice. Those mice were treated with pristane alone or combined with chloroquine. Hematological and biochemical parameters, macrophage phagocytic function, the oxidant/antioxidant index, cytokine for IFN-γ, TNF-α, IL-4, and IL-6, and the isotypes of IgG2a and IgG1 were determined. And the expression of T-bet/GATA-3 and IL-12/IL-10 mRNA in spleen were analyzed by real-time PCR. We found that pristane treatment for a period of 12 or 24 weeks triggered macrophage activation syndrome, characterized by hemophagocytosis in spleen and peripheral blood, enhanced lipid phagocytosis by peritoneal macrophages in vitro, erythropenia and leucopenia, increased anti-Smith, lactic dehydrogenase, triglyceride, and ferritin, as well as hypercytokinemia of IFN-γ, TNF-α, IL-4, and IL-6. In parallel, a significant increase in lipid peroxidation and a decrease in superoxide dismutase, glutathione, and catalase activity, as well as a skewed Th1/Th2 balance in spleen, were observed. However, chloroquine supplementation showed a remarkable amelioration of these abnormalities. Our data indicate that pristane administration induces macrophage activation, oxidative stress, and Th1/Th2 skewness, which can be attenuated by chloroquine.

Show MeSH
Related in: MedlinePlus