RRC ID 59881
Author Endo K, Kito H, Tanaka R, Kajikuri J, Tanaka S, Elboray EE, Suzuki T, Ohya S.
Title 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.
Journal Int J Mol Sci
Abstract 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)-1α 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-1α 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.
Volume 21(1)
Published 2019-12-19
DOI 10.3390/ijms21010038
PII ijms21010038
PMID 31861667
PMC PMC6981474
MeSH Animals Benzamides / pharmacology CD4-Positive T-Lymphocytes / metabolism* Cell Hypoxia Cell Line Dextran Sulfate / adverse effects Disease Models, Animal Gene Expression Regulation Humans Hypoxia-Inducible Factor 1, alpha Subunit / genetics* Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Inflammatory Bowel Diseases / chemically induced Inflammatory Bowel Diseases / genetics* Inflammatory Bowel Diseases / metabolism Mice Potassium Channels, Tandem Pore Domain / genetics* Potassium Channels, Tandem Pore Domain / metabolism Sirtuin 1 / genetics Sirtuin 1 / metabolism Thymocytes / cytology Thymocytes / metabolism
IF 4.183
Times Cited 0
Human and Animal Cells CTLL-2(RCB0637)