title: Peroxiredoxin V selectively regulates IL-6 production by modulating the Jak2-Stat5 pathway.
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.
authors.affiliation: Dental Science Research Institute and the BK21 Project, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea.
authors.forename: Hoon-In
authors.initials: HI
authors.lastname: Choi
authors.affiliation: Dental Science Research Institute and the BK21 Project, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea; Technical University of Dresden, Department of Medicine, Division of Vascular inflammation, 01307 Dresden, Germany.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Chung
authors.affiliation: Dental Science Research Institute and the BK21 Project, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea.
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Yang
authors.affiliation: Dental Science Research Institute and the BK21 Project, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea.
authors.forename: Lina
authors.initials: L
authors.lastname: Ren
authors.affiliation: Dental Science Research Institute and the BK21 Project, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea.
authors.forename: Sungoh
authors.initials: S
authors.lastname: Sohn
authors.affiliation: Department of Oral & Maxillofacial Surgery, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea.
authors.forename: Poo-Reun
authors.initials: PR
authors.lastname: Kim
authors.affiliation: Department of Oral & Maxillofacial Surgery, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea.
authors.forename: Min-Suk
authors.initials: MS
authors.lastname: Kook
authors.affiliation: Department of Microbiology and Genome Research Center for Enteropathogenic Bacteria, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Hyon E
authors.initials: HE
authors.lastname: Choy
authors.affiliation: Dental Science Research Institute and the BK21 Project, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea. Electronic address: thlee83@chonnam.ac.kr.
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Lee
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000276:immunology*; D047468:Immunoprecipitation; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000276:immunology; D053614:Janus Kinase 2 / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D054464:Peroxiredoxins / Q000276:immunology / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D050799:STAT5 Transcription Factor; D054464:Peroxiredoxins; C515975:Prdx5 protein, mouse; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2
keywords: CD14; G-CSF; H(2)O(2); IFN-β; IL-6; Jak2; Jak2/Stat5 pathway; LPS; MAL; MAPKs; MD2; N-acetyl-L-cysteine; NAC; NF-κB; Peroxiredoxin V; PrdxV; RANTES; ROS; SOCS1; Stat5; TLR4; TNF-α; TRAM; TRIF; TRIF-related adaptor molecule; Toll/I-1 receptor domain-containing adaptor inducing interferon-β; cluster of differentiation; granulocyte colony-stimulating factor; hydrogen peroxide; interferon β; interleukin 6; janus kinase 2; lipopolysaccaride; mitogen-activated protein kinases; myD88-adaptor-like protein; myeloid differentiation protein; nuclear factor kappa B; peroxiredoxin V; reactive oxygen species; regulated on activation, normal T-cell expressed, and secreted; signal transducer and activator of transcription 5; suppressor of cytokine signaling 1; toll like receptor 4; tumor necrosis factor α