Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8271403 | Free Radical Biology and Medicine | 2013 | 10 Pages |
Abstract
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.
Keywords
NF-κBmyeloid differentiation proteinPeroxiredoxin VMD2STAT5Janus Kinase 2SOCS1TLR4CD14JAK2N-acetyl-l-cysteineIFN-βNACMALLPSIL-6MAPKsROSTRIFHydrogen peroxideinterferon βinterleukin 6TRAMtumor necrosis factor αcluster of differentiationsuppressor of cytokine signaling 1granulocyte colony-stimulating factorG-CSFTNF-αnuclear factor kappa Bsignal transducer and activator of transcription 5lipopolysaccarideToll like receptor 4RANTESTRIF-related adaptor moleculeH2O2mitogen-activated protein kinasesReactive oxygen species
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Authors
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,