International immunopharmacology
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Int. Immunopharmacol. · May 2013
α-Lipoic acid attenuates LPS-induced cardiac dysfunction through a PI3K/Akt-dependent mechanism.
Myocardial dysfunction is an important manifestation of sepsis/septic shock. Activation of Phosphatidylinositol 3-kinase(PI3K)/protein kinase B (Akt) signaling pathway has been shown to improve cardiac performance during sepsis/septic shock. We have reported previously that α-lipoic acid (LA) activates PI3K/Akt pathway in neuronal cells. ⋯ More importantly, inhibition of PI3K/Akt signaling by Wortmannin (WM) completely abrogated the LA-induced protection in cardiac dysfunction following LPS challenge. Collectively, our results demonstrated that LA improved cardiac function during endotoxemia. The mechanism was through, at least in part, preserved activation of the PI3K/Akt signaling.
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Int. Immunopharmacol. · Mar 2013
Mobilization of progenitor cells into peripheral blood by gamma-tocotrienol: a promising radiation countermeasure.
Gamma-tocotrienol (GT3), a vitamin E isoform, is shown to induce high levels of granulocyte colony stimulating factor (G-CSF) in mice. G-CSF is a key cytokine used for stimulation of hematopoiesis, and mobilization of hematopoietic stem and progenitor cells into peripheral blood. GT3 is also shown to induce vascular endothelial growth factor (VEGF), another important cytokine necessary for vasculogenesis and endothelial progenitor mobilization. ⋯ Three groups of mice received vehicle, GT3 and GT3 plus AMD3100, a receptor antagonist used to enhance mobilization. GT3 induced significant mobilization of all three progenitor cell types compared to vehicle in peripheral blood; AMD3100 enhanced GT3-induced mobilization even further. Mobilization of progenitor cells in peripheral blood by GT3 indicates that GT3 can be used as an alternative to G-CSF and VGEF to mobilize HPCs and EPCs.
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Int. Immunopharmacol. · Feb 2013
Therapeutic effects of bone marrow-derived mesenchymal stem cells on pulmonary impact injury complicated with endotoxemia in rats.
Previous studies have demonstrated that acute lung injury (ALI) is associated with significant mortality and so far no effective pharmacotherapy is shown to reverse the natural progression. This study aims to investigate whether the transplantation of bone marrow derived mesenchymal stem cells (MSCs) might restore damaged pulmonary function and tissue structure in ALI. By using a sublethal chest impact injury plus endotoxemia model, MSCs were intravenously transplanted into the injured rats 2h after trauma. ⋯ Meanwhile, the secretions of pro-inflammatory TNF-α and IL-6 were alleviated, while the secretion of anti-inflammatory IL-10 was elevated. Engraftment of MSCs improved the pulmonary gas exchanges, alleviated the lung injury, and reduced the rats' mortality. These results suggested that the MSCs based measures might be a promising strategy in trauma and endotoxemia induced ALI treatment.
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Int. Immunopharmacol. · Feb 2013
CHP1002, a novel andrographolide derivative, inhibits pro-inflammatory inducible nitric oxide synthase and cyclooxygenase-2 expressions in RAW264.7 macrophages via up-regulation of heme oxygenase-1 expression.
Andrographolides, a type of diterpene lactone, are widely known to have anti-inflammatory and anti-oxidative properties. CHP1002, a synthetic derivative of andrographolide, has similar anti-inflammatory action in mouse ear swelling test and rat paw edema test. In the present study, the mechanism of anti-inflammatory effects of CHP1002 was investigated in RAW264.7 macrophages. ⋯ Down-regulation of LPS-induced iNOS and COX-2 expressions was partially reversed by the HO-1 inhibitor zinc protoporphyrin (ZnPP). In addition, CHP1002 significantly attenuated LPS-induced TNF-α, IL-1β and IL-6 production. CHP1002 effectively induced HO-1 and was capable of inhibiting some macrophage-derived pro-inflammatory mediators, which may be closely correlated with its anti-inflammatory action.
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Int. Immunopharmacol. · Dec 2012
Imbalance of Th17/Treg cells in mice with chronic cigarette smoke exposure.
Recent studies have revealed that autoimmune responses mediated by CD4(+) T cells may contribute to the development of chronic obstructive pulmonary disease (COPD). Meanwhile, imbalance of Th17/Treg has been reported to play a key role in the pathogenesis of autoimmune diseases. However, information on Th17/Treg balance in COPD is relatively limited. ⋯ Our study thus reveals that the Th17/Treg imbalance exists in mice with chronic CS exposure, suggesting its potential role in the breakdown of immune self-tolerance in COPD. Further research on regulation of Th17/Treg balance may provide insights into the development of new therapeutic targets for this disease.