Inflammation
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Thymol is a natural monoterpene phenol primarily found in thyme, oregano, and tangerine peel. It has been shown to possess anti-inflammatory property both in vivo and in vitro. In the present paper, we studied the anti-inflammatory effect of thymol in lipopolysaccharide (LPS)-stimulated mouse mammary epithelial cells (mMECs). ⋯ Furthermore, thymol blocked the phosphorylation of IκBα, NF-κB p65, ERK, JNK, and p38 mitogen-activated protein kinases (MAPKs) in LPS-stimulated mMECs. These results indicate that thymol exerted anti-inflammatory property in LPS-stimulated mMECs by interfering the activation of NF-κB and MAPK signaling pathways. Thereby, thymol may be a potential therapeutic agent against mastitis.
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Inflammatory cells, macrophages induced by lipopolysaccharide (LPS) stimulation, lead to the production of inflammatory cytokines, which are crucial to host defense. MicroRNAs are short noncoding RNAs that regulate key biological processes via suppression of gene expression at posttranscriptional levels. Recently, miR-146a has been shown to be involved in the regulation of immune and inflammatory responses. ⋯ Bioinformatics analyses predict that Notch1 is a potential target of miR-146a. Moreover, miR-146a overexpression in LPS-treated RAW264.7 macrophage cells did significantly decrease Notch1 mRNA and protein levels. These results suggested that miR-146a may function as a novel feedback negative regulator to LPS-induced production of inflammatory cytokines, at least in part, via inhibiting the expression of Notch1.
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Endotoxin tolerance is an important mechanism for preventing uncontrolled inflammatory cytokine production in bacterial sepsis. However, its molecular mechanisms remain largely unknown. It was reported that Twist-2 protein was a negative regulator for cytokine signaling by repressing the nuclear factor (NF)-κB-dependent cytokine pathway. ⋯ Moreover, the inhibitive effects partly weaken in KCs transfected with Twist-2 shRNA. Twist-2 was involved in endotoxin tolerance through inhibiting NF-κB trans-activation and cytokines transcriptional activities. It may be a new target for the clinical treatment of sepsis and other inflammatory diseases.
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Animal models have shown that mesenteric lymph plays important roles in the pathogenesis of endothelium injury in many critical ill states. Gut-derived septicemia and endothelium injury are the two key pathogenesis of heat stroke (HS); however, it is unclear whether mesenteric lymph is cytotoxic to endothelium in HS. HS rat models were prepared in a prewarmed incubator. ⋯ The effects of HS lymph on IL-6 production had a time course resembling that of the toxic effects of HS lymph on HUVEC. In vivo, when compared with HS rats, decreased CEC counts as well as lower serum vWF and TM concentrations were detected in HS-LDL rats. HS mesenteric lymph is probably harmful to vascular endothelium, which indicates that the modulation of mesenteric lymph may have some potential benefits to HS.
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Interleukin-1 receptor-associated kinase (IRAK1) is a key regulatory protein in TLR/IL1R-mediated cell activation during inflammatory response. Studies indicated that pending on the nature of the used inflammatory model, downregulation of IRAK1 may be beneficial or detrimental. However, the role of IRAK1 in affecting outcome in polymicrobial sepsis is unknown. ⋯ TLR7/8-mediated IL-6, IL1β, and IL-10 production was also blunted in IRAK1 macrophages as compared to WT. The study shows that IRAK1 deficiency impacts multiple TLR-dependent pathways and decreases early cytokine responses following polymicrobial sepsis. The delayed inflammatory response caused by the lack of IRAK1 expression is beneficial, as it manifests a marked increased chance of survival after polymicrobial sepsis.