title: NLRP6 facilitates the interaction between TAB2/3 and TRIM38 in rheumatoid arthritis fibroblast-like synoviocytes.
abstract: In the present study, we investigated the role of nucleotide oligomerization domain-like receptor family pyrin domain containing 6 (NLRP6) in rheumatoid arthritis (RA) and explored the underlying mechanism. We found that both mRNA and protein levels of NLRP6 are attenuated in synovial tissues and fibroblast-like synoviocytes (FLS) of RA patients compared to patients with osteoarthritis. We also observed that pro-inflammatory cytokine production is decreased and nuclear factor-kappa B activation is inhibited in NLRP6-overexpressing RA-FLS. Furthermore, we found that NLRP6 overexpression promotes transforming growth factor-b-activated kinase 1-binding protein 2/3 lysosome-dependent degradation, and we provide evidence showing that NLRP6 plays the role of providing the docking site to facilitate the interaction between transforming growth factor-b-activated kinase 1-binding protein 2/3 and tripartite motif 38 in RA-FLS.
authors.affiliation: Department of Orthopedics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Orthopedics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhengqiang
authors.initials: Z
authors.lastname: Luo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D017930:Genes, Reporter; D006801:Humans; D047468:Immunoprecipitation; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000070918:Synoviocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000070584:Tripartite Motif Proteins; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; C468563:NLRP6 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; C410585:TAB2 protein, human; C481053:TAB3 protein, human; C439524:TNF protein, human; D000070584:Tripartite Motif Proteins; D014409:Tumor Necrosis Factor-alpha; C106984:TRIM38 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: NF-κB; NLRP6; TAB2/3; fibroblast-like synoviocytes; rheumatoid arthritis