International immunopharmacology
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Int. Immunopharmacol. · Mar 2016
MiR-146a modulates macrophage polarization by inhibiting Notch1 pathway in RAW264.7 macrophages.
Macrophages are heterogeneous and plastic cells which are able to undergo dynamic transition between M1 and M2 polarized phenotypes in response to the microenvironment signals. However, the underlying molecular mechanisms of macrophage polarization are still obscure. In the current study, it was revealed that miR-146a might play a pivotal role in macrophage polarization. ⋯ Mechanistically, it was revealed that miR-146a modulated macrophage polarization by targeting Notch1. Of note, PPARγ was responsible as another target for miR-146a-mediated macrophage polarization. Taken together, it was suggested that miR-146a might serve as a molecular regulator in macrophage polarization and is a potential therapeutic target for inflammatory diseases.
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Int. Immunopharmacol. · Mar 2016
Protective effects of pogostone against LPS-induced acute lung injury in mice via regulation of Keap1-Nrf2/NF-κB signaling pathways.
Pogostone, a major component of Pogostemon cablin, has been demonstrated to possess antibacterial, anti-fungal, immunosuppressive and anti-inflammatory properties. To investigate the potential therapeutic effect of pogostone on lipopolysaccharide (LPS)-induced acute lung injury (ALI), mice were pretreated with pogostone prior to LPS exposure. After LPS challenge, the lungs were excised and the histological changes, wet to dry weight ratios, MPO activity reflecting neutrophil infiltration, and MDA activity reflecting oxidative stress were examined. ⋯ Furthermore, pretreatment with pogostone enhanced the Nrf2 dependent genes including NQO-1, GCLC and HO-1 but suppressed NF-κB regulated genes including TNF-α, IL-1β and IL-6. The mechanism behind the protective effect was correlated with its regulation on the balance between Keap1-Nrf2 and NF-κB signaling pathways. Therefore, pogostone may be considered as a potential therapeutic agent for preventing and treating ALI.
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Int. Immunopharmacol. · Mar 2016
Consistency and pathophysiological characterization of a rat polymicrobial sepsis model via the improved cecal ligation and puncture surgery.
Sepsis is the leading cause of death for critical ill patients and an essential focus in immunopharmacological research. The cecal ligation and puncture (CLP) model is regarded as a golden standard model for sepsis study. However, this animal model is easily affected by variability problems and dramatically affects pharmacological evaluation of anti-sepsis therapies, which requires standardized procedures and stable outcomes. ⋯ In contrast to traditional syringe needles, these three-edged needles ensured more stable outcomes in repetitive groups. Furthermore, increased severity was found to be consistent with the enlarged needle size, as shown by the elevated mortality, increased proinflammatory cytokines, abnormal coagulation, worsen acidosis and more severe acute lung injury. In conclusion, application of the newly-developed three-edged needles provides a simple and feasible method to improve stability when conducting CLP surgery, which is significant for pharmacological studies on sepsis.