The importance of Ca 2+ signalling and temperature in the context of T cell activation is well known. However, the molecular identities of key players involved in such critical regulations are still unknown. In this work we explored the endogenous expression of transient receptor potential vanilloid (TRPV) channels, a group of thermosensitive and non-selective cation channels, in T cells. Using flow cytometry and confocal microscopy, we demonstrate that members belonging to the TRPV subfamily are expressed endogenously in the human T cell line Jurkat, in primary human T cells and in primary murine splenic T cells. We also demonstrate that TRPV1-and TRPV4-specific agonists, namely resiniferatoxin and 4a-phorbol-12,13-didecanoate, can cause Ca 2+ influx in T cells. Moreover, our results show that expression of these channels can be upregulated in T cells during concanavalin A-driven mitogenic and anti-CD3/CD28 stimulated TCR activation of T cells. By specific blocking of TRPV1 and TRPV4 channels, we found that these TRPV inhibitors may regulate mitogenic and T cell receptor mediated T cell activation and effector cytokine(s) production by suppressing tumour necrosis factor, interleukin-2 and interferon-c release. These results may have broad implications in the context of cell-mediated immunity, especially T cell responses and their regulations, neuro-immune interactions and molecular understanding of channelopathies.
Oxidative stress is implicated in both hypo- and hyper-thyroid conditions. In the present study an attempt has been made to elucidate possible interaction between vitamin E or/and curcumin (two established antioxidants) with active portion (redox signaling intervening region) of nuclear factor erythroid 2-related factor 2 (NRF2) as a mechanism to alleviate oxidative stress in rat heart under altered thyroid states. Fifty Wistar strain rats were divided into two clusters (Cluster A: hypothyroidism; Cluster B: hyperthyroidism). The hypo- (0.05% (w/v) propylthiouracil in drinking water) and hyper- (0.0012% (w/v) T4 in drinking water) thyroid rats in both clusters were supplemented orally with antioxidants (vitamin E or/and curcumin) for 30 days. Interactive least count difference and principal component analyses indicated increase in lipid peroxidation, reduced glutathione level, alteration in the activities and protein expression of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase under altered thyroid states. However, the expression of stress survival molecules; nuclear factor κB (NFκB) and the serine-threonine kinase B (Akt), in hyper-thyroidism only points towards different mechanisms responsible for either condition. Co-administration of vitamin E and curcumin showed better result in attenuating expression of mammalian target for rapamycin (mTOR), restoration of total protein content and biological activity of Ca
2+
ATPase in hyperthyroid rats, whereas, their individual treatment showed partial restoration. Since NRF2 is responsible for activation of antioxidant response element and subsequent expression of antioxidant enzymes, possible interactions of both vitamin E or/and curcumin with the antioxidant enzymes, NRF2 and its regulator Kelch ECH associating protein (KEAP1) were studied
in silico
. For the first time, a modeled active portion of the zipped protein NRF2 indicated its interaction with both vitamin E and curcumin. Further, curcumin and vitamin E complex showed
in silico
interaction with KEAP1. Reduction of oxidative stress by curcumin and/or vitamin E may be due to modulation of NRF2 and KEAP1 function in rat heart under altered thyroid states.
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