NLRP6 facilitates the interaction between TAB2/3 and TRIM38 in rheumatoid arthritis fibroblast-like synoviocytes

FEBS Lett. 2017 Apr;591(8):1141-1149. doi: 10.1002/1873-3468.12622. Epub 2017 Mar 30.

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.

Keywords: NF-κB; NLRP6; TAB2/3; fibroblast-like synoviocytes; rheumatoid arthritis.

Publication types

  • Comparative Study

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Down-Regulation
  • Genes, Reporter
  • Humans
  • Immunoprecipitation
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Osteoarthritis / immunology
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Protein Interaction Domains and Motifs
  • RNA Interference
  • RNA, Messenger / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Synovial Membrane / immunology
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • Synoviocytes / immunology
  • Synoviocytes / metabolism*
  • Synoviocytes / pathology
  • Tripartite Motif Proteins
  • Tumor Necrosis Factor-alpha / metabolism
  • Ubiquitin-Protein Ligases

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Intracellular Signaling Peptides and Proteins
  • NLRP6 protein, human
  • RNA, Messenger
  • Recombinant Proteins
  • TAB2 protein, human
  • TAB3 protein, human
  • TNF protein, human
  • Tripartite Motif Proteins
  • Tumor Necrosis Factor-alpha
  • TRIM38 protein, human
  • Ubiquitin-Protein Ligases