| Autor: |
Ju-Won Jang, Pham Xuan Thuy, Jae-Wook Lee, Eun-Yi Moon |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Cell Death and Disease, Vol 12, Iss 4, Pp 1-12 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2041-4889 |
| DOI: |
10.1038/s41419-021-03615-w |
| Popis: |
Abstract B cells that interact with T cells play a role in regulating the defense function by producing antibodies and inflammatory cytokines. C-X-C chemokine receptor type 4 (CXCR4) is a specific receptor for stromal cell-derived factor 1 (SDF-1) that controls various B cell functions. Here, we investigated whether CXCR4 regulates B cell viability by inducing hypoxia-inducible factor (HIF)-1α and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) under a hypoxic condition in WiL2-NS human B cells. Nrf2 and CXCR4 expressions increased significantly when WiL2-NS cells were incubated under a hypoxic condition. Interfering with CXCR4 expression using CXCR4-siRNA inhibited cell viability. CXCR4 expression also decreased after treatment with a HIF inhibitor under the hypoxic condition, leading to inhibited cell viability. Increased reactive oxygen species (ROS) levels and the expression of HIF-1α and Nrf2 decreased under the hypoxic condition following incubation with N-acetylcysteine, a ROS scavenger, which was associated with a decrease in CXCR4 expression. CXCR4 expression was augmented by overexpressing Nrf2 after transfecting the pcDNA3.1-Nrf2 plasmid. CXCR4 expression decreased and HIF-1α accumulation decreased when Nrf2 was inhibited by doxycycline in tet-shNrf2-expressed stable cells. Nrf2 or HIF-1α bound from −718 to −561 of the CXCR4 gene promoter as judged by a chromatin immunoprecipitation assay. Taken together, these data show that B cell viability under a hypoxic condition could be regulated by CXCR4 expression through binding of HIF-1α and Nrf2 to the CXCR4 gene promoter cooperatively. These results suggest that CXCR4 could be an additional therapeutic target to control B cells with roles at disease sites under hypoxic conditions. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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