Peroxiredoxin V selectively regulates IL-6 production by modulating the Jak2-Stat5 pathway

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• 作者：Hoon-In Choi ; Kyoung-Jin Chung ; Hee-Young Yang ; Lina Ren ; Sungoh Sohn ; Poo-Reun Kim ; Min-Suk Kook ; Hyon E. Choy ; Tae-Hoon Lee
• 关键词：PrdxV ; peroxiredoxin V ; LPS ; lipopolysaccaride ; IL-6 ; interleukin 6 ; Jak2 ; janus kinase 2 ; Stat5 ; signal transducer and activator of transcription 5 ; SOCS1 ; suppressor of cytokine signaling 1 ; TNF-伪 ; tumor necrosis factor 伪 ; IFN-尾 ; interferon 尾 ; RANTES ; regulated on activation ; normal T-cell expressed ; and secreted ; G-CSF ; granulocyte colony-stimulating factor ; TLR4 ; toll like receptor 4 ; MD2 ; myeloid differentiation protein ; CD14 ; cluster of differentiation ; MAL ; myD88-adaptor-like protein
• 刊名：Free Radical Biology and Medicine
• 出版年：December, 2013
• 年：2013
• 卷：65
• 期：Complete
• 页码：270-279
• 全文大小：1114 K

文摘

Mammalian peroxiredoxin V (PrdxV) is a multifunctional protein that protects cells from DNA damage and inhibits stress-induced apoptosis. However, PrdxV is also known to be involved in modulating lipopolysaccharide (LPS)-induced host cell signaling, but its precise role is not fully understood. In this study, we used stably transfected RAW264.7 cells and transiently transfected 293-mTLR4-MD2-CD14 cells expressing wild-type (WT) or mutant (C48S) PrdxV to characterize the function and mechanism of action of PrdxV in LPS-induced immune responses. We found that PrdxV selectively reduces production of interleukin 6 (IL-6) by inhibiting activation of signal transducer and activator of transcription 5 (Stat5) through interaction with Jak2. Notably, this activity of PrdxV was dependent on its catalytic Cys48 residue, but not its peroxidase activity. The binding of to Jak2 effectively inhibited Jak2 phosphorylation, but PrdxV did not act as efficiently as SOCS1 (suppressor of cytokine signaling 1). Our results suggest that PrdxV is a key mediator contributing to the regulation of LPS/TLR4-induced immune responses.