9 research outputs found
Different Mitogen-Mediated Beta-Adrenergic Receptor Modulation in Murine T Lymphocytes Depending on the Thyroid Status
Combination treatment of mice with crx-153 (nortriptyline and desloratadine) decreases the severity of experimental autoimmune encephalomyelitis
Impact of Postoperative Infection on Long-Term Survival After Potentially Curative Resection for Gastric Cancer
Cerebellar Fastigial Nuclear Glutamatergic Neurons Regulate Immune Function via Hypothalamic and Sympathetic Pathways
Mitochondrial Superoxide Signaling Contributes to Norepinephrine-Mediated T-Lymphocyte Cytokine Profiles
<div><p>Norepinephrine (NE) produces multifaceted regulatory patterns in T-lymphocytes. Recently, we have shown that NE utilizes redox signaling as evidenced by increased superoxide (O<sub>2</sub><sup>●-</sup>) causally linked to the observed changes in these cells; however, the source of this reactive oxygen species (ROS) remains elusive. Herein, we hypothesized that the source of increased O<sub>2</sub><sup>●-</sup> in NE-stimulated T-lymphocytes is due to disruption of mitochondrial bioenergetics. To address this hypothesis, we utilized purified mouse splenic CD4+ and CD8+ T-lymphocytes stimulated with NE and assessed O<sub>2</sub><sup>●-</sup> levels, mitochondrial metabolism, cellular proliferation, and cytokine profiles. We demonstrate that the increase in O<sub>2</sub><sup>●-</sup> levels in response to NE is time-dependent and occurs at later points of T-lymphocyte activation. Moreover, the source of O<sub>2</sub><sup>●-</sup> was indeed the mitochondria as evidenced by enhanced MitoSOX Red oxidation as well as abrogation of this signal by the addition of the mitochondrial-targeted O<sub>2</sub><sup>●-</sup>-scavenging antioxidant MitoTempol. NE-stimulated T-lymphocytes also demonstrated decreased mitochondrial respiratory capacity, which suggests disruption of mitochondrial metabolism and the potential source of increased mitochondrial O<sub>2</sub><sup>●-</sup>. The effects of NE in regards to redox signaling appear to be adrenergic receptor-dependent as specific receptor antagonists could reverse the increase in O<sub>2</sub><sup>●-</sup>; however, differential receptors regulating these processes were observed in CD4+ versus CD8+ T-lymphocytes. Finally, mitochondrial O<sub>2</sub><sup>●-</sup> was shown to be mechanistic to the NE-mediated T-lymphocyte phenotype as supplementation of MitoTempol could reverse specific changes in cytokine expression observed with NE treatment. Overall, these studies indicate that mitochondrial metabolism and O<sub>2</sub><sup>●-</sup>-mediated redox signaling play a regulatory role in the T-lymphocyte response to NE.</p></div