Inflammation
-
Blunt chest (thoracic) trauma (TxT) and hemorrhagic shock (HS)-induced local and systemic inflammation with increased neutrophil activity often result in an impaired organ function. Next to increasing the trauma risk, binge drinking causes anti-inflammatory effects due to immunomodulatory properties of alcohol (ethanol, EtOH). The impact of clinically relevant acute binge drinking scenario on local and systemic inflammatory changes, notably regarding the activity and longevity of leukocytes, has been analyzed in a combinatory trauma model of TxT + H/R. ⋯ Apoptosis was prolonged only in PMN after TxT + H/R and was further prolonged by EtOH, an effect that was observed in sham animals as a trend as well. Acute EtOH exposure inhibits the activation of circulating leukocytes after trauma compared to controls. These EtOH-driven systemic changes may be associated with reduced infiltration with PMN after trauma as well as reduced local tissue inflammation.
-
Mechanical ventilation (MV) can augment sepsis-induced organ injury. Previous studies indicate that human mesenchymal stem cells (hMSCs) have immune-modulatory effect. We hypothesize that human adipose tissue-derived stromal cells (hADSCs) could attenuate MV and sepsis-induced organ injury. ⋯ Real-time quantitative PCR was used to analyze mRNA of IL-6 and tumor necrosis factor-α (TNF-α). hADSC treatment increased survival rate of septic mice with MV. hADSCs attenuated dysfunction of the liver and kidney and decreased lung inflammation and tissue injury of the liver and lung. IL-6 level in BALF and TNF-α and IL-6 mRNA expression in the tissue of the lung, liver, and kidney were significantly reduced by hADSC treatment. MV with conventional tidal volume aggravates CLP-induced multiple organ injuries. hADSCs inhibited the compound injuries possibly through modulation of immune responses.
-
Hyperhomocysteinemia (HHCY) has been recognized as an independent risk factor for atherosclerosis and plays a vital role in the development of atherosclerosis. Catalpol, an iridoid glucoside extracted from the root of Rehmannia glutinosa, can produce anti-inflammatory, anti-oxidant, anti-tumor, and dopaminergic neurons protecting effects. This study aimed to determine the protecting effects of catalpol against homocysteine (HCY)-induced injuries in human aortic endothelial cells (HAECs) and uncover the underlying mechanisms: 1. ⋯ The inhibitor of NF-κB PDTC also reduced the effects of catalpol inhibiting the expressions of Nox4 and GRP78. Furthermore, the effect of catalpol inhibiting the over-generation of ROS was reduced by Nox4 siRNA. Catalpol could ameliorate HCY-induced oxidation, cells apoptosis and inflammation in HAECs possibly by inhibiting Nox4/NF-κB and ER stress.
-
Increasing evidence shows miR-155 plays an important role in regulating inflammatory processes in systemic lupus erythematosus (SLE), especially in lupus nephritis (LN). Because the chemokine CXCL13 is implicated in the pathogenesis of LN, here we examined whether miR-155 can modulate the activity of CXCL13 or its receptor CXCR5. We determined the expression of CXCL13 in normal and MRL/lpr mice and found elevated levels of CXCL13 in the kidneys of MRL/lpr mice compared with normal kidneys. ⋯ Transfection of the miR-155 mimic into CXCL13-treated HRMCs resulted in a significantly reduced proliferation rate of HRMCs as measured by the cell-counting assay and flow cytometry. Moreover, increased intracellular miR-155 also led to decreased phosphorylation of ERK and TGF-β1 production. Together, these results revealed that miR-155 may play a role in the pathogenesis of LN.
-
We have found earlier that Tubastatin A (TubA), a selective inhibitor of histone deacetylase 6 (HDAC6), improves survival in a mouse model of lethal cecal ligation and puncture (CLP)-induced sepsis. However, the underlying mechanisms have not been fully established. This study sought to test the hypothesis that TubA could affect both lung and splenic functions. ⋯ Treatment with TubA restored the percentage of B lymphocytes, and significantly increased percentages of innate immune cells and macrophages compared to the vehicle-treated CLP group. Moreover, TubA significantly decreased the bacterial load in the spleen, and improved the phagocytic ability of RAW264.7 murine macrophages in vitro. Such findings may help to explain the beneficial effects of TubA treatment in a model of lethal sepsis, as previously reported.