Presence of TRPV3 in macrophage lysosomes helps in skin wound healing against bacterial infection.

Transient Receptor Potential Vanilloid subtype 3 (TRPV3) is a non-selective cation channel that is known to be activated by physiological temperature and endogenous ligands. Involvement of TRPV3 in different skin functions has been reported. In this work, we demonstrate that activation of TRPV3 by FPP, an endogenous ligand enhances skin wound healing and bacterial clearance there. We report for the first time that TRPV3 is endogenously expressed in macrophages and activation of TRPV3 results in efficient bacterial clearance. At the subcellular level, TRPV3 is present in the lysosome and also in the nucleolus. We demonstrate that pharmacological modulation of TRPV3 protects lysosomal functions at hyperthermic shock conditions. The localization of TRPV3 at the nucleolus is specific, more in case of LPS-treatment and dynamic with respect to the cell signalling. We demonstrate that at certain conditions, the nucleolar localization of TRPV3 is correlated with the presence of TRPV3 at the lysosome and with the cellular stress in general. We propose that TRPV3 act as a lysosomal regulator and sensor for cellular stress. These findings may have broad implications in understanding the cellular stress and TRPV3-induced channelopathies and may have clinical relevance to skin infection treatment.

Inhibition of transient receptor potential vanilloid 1 (TRPV1) channel regulates chikungunya virus infection in macrophages.

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-κB (p65) expression and nuclear localization. However, both activation and inhibition of TRPV1 were found to enhance the expression and nuclear localization of pNF-κB (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.