Anti-TNF monoclonal antibody, clone FQ2196Z

Chikungunya virus (CHIKV), a virus that induces pathogenic inflammatory host immune responses, is re-emerging worldwide, and there are currently no established antiviral control measures. Transient receptor potential vanilloid 1 (TRPV1), a non-selective -Ca2+-permeable ion channel, has been found to regulate various host inflammatory responses including several viral infections. Immune responses to CHIKV infection in host macrophages have been reported recently. However, the possible involvement of TRPV1 during CHIKV infection in host macrophages has not been studied. Here, we investigated the possible role of TRPV1 in CHIKV infection of the macrophage cell line RAW 264.7. It was found that CHIKV infection upregulates TRPV1 expression in macrophages. To confirm this observation, the TRPV1- specific modulators 5'-iodoresiniferatoxin (5' -IRTX, a TRPV1 antagonist) and resiniferatoxin (RTX, a TRPV1 agonist) were used. Our results indicated that TRPV1 inhibition leads to a reduction in CHIKV infection, whereas TRPV1 activation significantly enhances CHIKV infection. Using a plaque assay and a time-of-addition assay, it was observed that functional modulation of TRPV1 affects the early stages of the viral lifecycle in RAW 264.7 cells. Moreover, CHIKV infection was found to induce of pNF-.B (p65) expression and nuclear localization. However, both activation and inhibition of TRPV1 were found to enhance the expression and nuclear localization of pNF-.B (p65) and production of pro-inflammatory TNF and IL-6 during CHIKV infection. In addition, it was demonstrated by -Ca2+ imaging that TRPV1 regulates -Ca2+ influx during CHIKV infection. Hence, the current findings highlight a potentially important regulatory role of TRPV1 during CHIKV infection in macrophages. This study might also have broad implications in the context of other viral infections as well.

Ambient particulate matter (PM2.5)-induced metabolic syndromes is a critical contributor to the pathological processes of neurological diseases, but the underlying molecular mechanisms remain poorly understood. The rhomboid 5 homolog 2 (Rhbdf2), an essential regulator in the production of TNF-alpha, has recently been confirmed to exhibit a key role in regulating inflammation-associated diseases. Thus, we examined whether Rhbdf2 contributes to hypothalamic inflammation via NF-kappa B associated inflammation activation in long-term PM2.5-exposed mice. Specifically, proopiomelanocortin-specific Rhbdf2 deficiency (Rhbdf2(Pomc)) and corresponding littermates control mice were used for the current study. After 24 weeks of PM2.5 inhalation, systemic-metabolism disorder was confirmed in WT mice in terms of impaired glucose tolerance, increased insulin resistance, and high blood pressure. Markedly, PM2.5-treated Rhbdf2(Pomc) mice displayed a significantly opposite trend in these parameters compared with those of the controls group. We next confirmed hypothalamic injury accompanied by abnormal POMC neurons loss, as indicated by increased inflammatory cytokines, chemokines, and oxidative-stress levels and decreased antioxidant activity. These results were further supported by blood routine examination. In summary, our findings suggest that Rhbdf2 plays an important role in exacerbating PM2.5-stimulated POMC neurons loss associated hypothalamic injury, thus providing a possible target for blocking pathological development of air pollution-associated diseases.