| First Author | Endo K | Year | 2019 |
| Journal | Int J Mol Sci | Volume | 21 |
| Issue | 1 | PubMed ID | 31861667 |
| Mgi Jnum | J:292304 | Mgi Id | MGI:6435591 |
| Doi | 10.3390/ijms21010038 | Citation | Endo K, et al. (2019) Possible Contribution of Inflammation-Associated Hypoxia to Increased K2P5.1 K(+) Channel Expression in CD4(+) T cells of the Mouse Model for Inflammatory Bowel Disease. Int J Mol Sci 21(1):38 |
| abstractText | Previous studies have reported the up-regulation of the two-pore domain K(+) channel K2P5.1 in the CD4(+) T cells of patients with multiple sclerosis (MS) and rheumatoid arthritis (RA), as well as in a mouse model of inflammatory bowel disease (IBD). However, the mechanisms underlying this up-regulation remain unclear. Inflammation-associated hypoxia is involved in the pathogenesis of autoimmune diseases, such as IBD, MS, and RA, and T cells are exposed to a hypoxic environment during their recruitment from inflamed tissues to secondary lymphoid tissues. We herein investigated whether inflammation-associated hypoxia is attributable to the increased expression and activity of K2P5.1 in the splenic CD4(+) T cells of chemically-induced IBD model mice. Significant increases in hypoxia-inducible factor (HIF)-1alpha transcripts and proteins were found in the splenic CD4(+) T cells of the IBD model. In the activated splenic CD4(+) T cells, hypoxia (1.5% O2) increased K2P5.1 expression and activity, whereas a treatment with the HIF inhibitor FM19G11 but not the selective HIF-2 inhibitor exerted the opposite effect. Hypoxia-exposed K2P5.1 up-regulation was also detected in stimulated thymocytes and the mouse T-cell line. The class III histone deacetylase sirtuin-1 (SIRT1) is a downstream molecule of HIF-1alpha signaling. We examined the effects of the SIRT1 inhibitor NCO-01 on K2P5.1 transcription in activated CD4(+) T cells, and we found no significant effects on the K2P5.1 transcription. No acute compensatory responses of K2P3.1-K2P5.1 up-regulation were found in the CD4(+) T cells of the IBD model and the hypoxia-exposed T cells. Collectively, these results suggest a mechanism for K2P5.1 up-regulation via HIF-1 in the CD4(+) T cells of the IBD model. |
