Hypoxia-inducible Factor-1α Suppresses the Innate Immune Response in Cultured Human Proximal Tubular Cells.

Autor: DAIKI NAGAWA, MICHIKO SHIMADA, MASAMICHI NAKATA, IKUYO NARITA-KINJO, TAKESHI FUJITA, REIICHI MURAKAMI, NORIO NAKAMURA, HIROFUMI TOMITA
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Zdroj: In Vivo; Nov/Dec2023, Vol. 37 Issue 6, p2437-2446, 10p
Abstrakt: Background/Aim: Retinoic acid-inducible gene (RIG)-I like receptors (RLRs) are expressed on renal proximal tubular epithelial cells (RPTECs) in viral nephropathy, indicating the presence of RLR-mediated innate immune responses in RPTECs. Hypoxia is also known to affect innate immunity. This study investigated the effects of hypoxia, and hypoxia-inducible factor (HIF) on innate immunity in RPTECs. Materials and Methods: Primary human RPTECs were cultured under normoxic or hypoxic conditions and treated with a synthetic analog of doublestranded RNA (polyIC). The expression levels of RIG-I and MDA5, as RLRs, and IFNβ, IL6, and TNFα, as inflammatory mediators were evaluated using quantitative reverse transcription-polymerase chain reaction, western blotting, and lactate dehydrogenase activity (LDH) assays. To further investigate the role of hypoxia, a small interfering RNA was used to knockdown HIF1α. Results: Under normoxic conditions, polyIC increased RIG-I, MDA5, and IFNβ mRNA expression in RPTECs by, 9.4±0.4-, 10.8±0.5-, and 4.0±0.1- fold, respectively, compared to control, and by 5.4±0.1-, 7.4±0.1-, and 2.4±0.3-fold, respectively, under hypoxic conditions, the rate of increase was lower than that under normoxic conditions (p<0.01). Protein expression showed a similar trend. Under hypoxic conditions, polyIC treatment with HIF1α knockdown in RPTECs increased RIG-I, MDA5, and IFNβ mRNA expression by 3.1±0.5-, 2.9±0.4-, and 6.1±0.4-fold, respectively, and cytotoxicity, demonstrated by LDH assay, was increased compared to that without knockdown (all p<0.01). Conclusion: Hypoxia suppresses polyIC-induced RLRs mediated innate immune responses in RPTECs via HIF1α. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index