Toll-like receptors (TLRs) have critical roles in innate immunity and inflammation and the detailed mechanisms by which TLR signaling is fine tuned remain unclear. Keratin 8 (CK8) belongs to the type II keratin family and is the major compontent of the intermediate filaments of simple or single-layered epithelia. Here we report that down-regulation of CK8 in mice enhanced TLR-mediated responses, rendering mice more susceptible to lipopolysaccharide (LPS)-induced endotoxin shock and Escherichia coli–caused septic peritonitis with reduced survival, elevated levels of inflammation cytokines and more severe tissue damage. We found that CK8 suppressed TLR-induced nuclear factor (NF)-κB activation and interacted with the adaptor tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) to prevent its polyubiquitination. Our findings demonstrate a novel role of CK8 in negative regulation of TLR/NF-κB signaling and highlight a previously unidentified nonclassical function for CK8 in limiting inflammatory responses.

Objective and Background: To study the relationship between periodontitis and vascular calcification by establishing rat model of chronic periodontitis and vascular calcification. Methods: Forty male Wistar rats were divided into four groups randomly: control group, periodontitis group, vascular calcification group, and compound periodontitis and calcification group. Each group rats accepted the corresponding manages to establish the animal model. Clinical examinations and hematoxylin and eosin staining of periodontal tissue were taken to test the periodontal model; calcium assay, alkaline phosphatase activity, expression of mineral-related factors including osteopontin, alkaline phosphatase, core-binding factor-α1 and bone sialoprotein, hematoxylin and eosin staining and von Kossa staining of vascular tissue were taken to test the vascular calcification model; inflammatory factors including C-reactive protein, interleukin-1β, tumor necrosis factor-α, interleukin-6, prostaglandin E2, and serum lipid in serum were also detected at the same time. Results: The rat model was established. Inflammation of periodontal tissue and alveolar bone resorption in compound group and periodontitis group were more obvious than those in control group and vascular calcification group (P < .05). However, the calcium assay, alkaline phosphatase activity, and mineralized deposition in vascular calcification group and compound group were higher than those in control group and periodontitis group (P < .05), and compound group were the highest (P < .05); as for serum lipid, the level of total cholesterol and low-density lipoprotein-cholesterol in compound group and vascular calcification group were higher than that in control group and periodontitis group (P < .05), and compound group was the highest (P <.05); but the level of high-density lipoprotein cholesterol was higher in control group and periodontitis group. Inflammatory factors expression in serum were higher in compound group and periodontitis group, while mineral-related factors expression were higher in compound group and vascular calcification group.

Microwave radiation could increase the expression of pro-inflammatory cytokines in rat Sertoli cells, which may impair spermatogenesis. However, the mechanisms that microwave radiation induces the cytokine expression in Sertoli cells remain to be clarified. The activation of TLRs by their ligands can trigger a common signalling pathway to upregulate inflammatory cytokines such as IL-1, IL-6, IL-12 and TNF-α. Microwave radiation can increase the expression of TLRs in lymphocytes. The purpose of this study was to determine the effect of microwave radiation on the TLRs in rat testis. We focus on the effect of TLR2-5 (which is expressed relatively highly) by microwave radiation. The results showed that the expression of TLR2-5 and the pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) was increased both in mRNA and in protein. Furthermore, p-p38, p-ERK1/2, p-JNK and p-NF-κB p65, the key factors of TLR signalling, were also elevated by microwave exposure. And the NF-κB can be induced more dominantly. These results suggest that TLRs signalling can be activated by microwave radiation in testis, which may provide the molecular basis for the in-depth study.

The effect of miR-124 on the proliferation and differentiation of brain glioma stem cells and Nogo/NgR signaling pathway were investigated. miR-124 mimic, miR-124 inhibitor and miR-control expression vector were designed and produced to transfect U87 glioma stem cells. The results of transfection were tested via RT-qPCR and the expression of protein was detected by western blot analysis. Cell proliferation was detected by MTT proliferation and the proportion of CD133+ cells was detected by immunomagnetic beads to determine cell differentiation. The correlation between miR-124 and Nogo-A, and NgR protein expression was analyzed by Spearman correlation analysis. The relative expression of miR-124 in cells of miR-124 mimic group was significantly higher than that of miR-124 inhibitor and miR-control groups (P<0.05). The relative expression of Nogo-A and NgR protein in cells of the miR-124 mimic group was significantly lower than that of miR-124 inhibitor and miR-control groups (P<0.05). Absorbance values of the cells in the miR-124 mimic and miR-control groups were significantly lower than those in the miR-124 inhibitor group at each time point (P<0.05), while the values of the cells in the miR-124 mimic group were significantly lower than that in miR-control group (P<0.05). The level of CD133+ cells in miR-124 mimic group was significantly lower than that in miR-124 inhibitor and miR-control groups (P<0.05), while the level of CD133+ cells in miR-124 inhibitor group was higher than that in miR-control group (P<0.05). Correlation analysis revealed that there was a negative correlation between miR-124 and the expression of Nogo-A and NgR protein (P<0.05). miR-124 may participate in the differentiation of brain glioma stem cells through the Nogo/NgR pathway, which may bring a new direction for the clinical treatment of brain glioma.