title: Overexpressed NLRC3 acts as an anti-inflammatory cytosolic protein.
abstract: The novel nucleotide oligomerization domain (NOD)-like receptor (NLR) with a caspase activation and recruitment domain (CARD) 3 (NLRC3) protein belongs to the NLR family of cytosolic pathogen recognition receptors. NLRC3 has the characteristic NOD and leucine-rich repeat configuration with a less well defined CARD. T lymphocytes are known to have high NLRC3 expression, which may be involved in suppression of T cell activation. Here, we report that NLRC3 is a cytoplasmic protein that negatively regulates pro-IL-1β maturation. Among well-known inflammasome components, NLRC3 can interact with apoptosis-associated speck-like protein containing a CARD (ASC) and caspases 1 and 5. Transient transfection of NLRC3 into stable EGFP-ASC-expressing HEK293FT cells reduces NLR family, pyrin domain-containing 3 (NLRP3)/cryopyrin-induced formation of ASC specks in a dose- and time-dependent manner. This suggests that NLRC3 can regulate ASC speck formation, caspase-1 activation and IL-1β maturation. We show for the first time that inflammasome-like complexes assemble when caspase-1 and ASC are cotransfected together with NLRC3 in HEK293FT cells. However, overexpression of NLRC3 with NLRP3/cryopyrin inflammasome components suppresses pro-caspase-1 cleavage and IL-1β processing. Our study suggests that NLRC3 negatively regulates inflammatory responses.
authors.affiliation: Department of Molecular Biology and Genetics, Apoptosis and Cancer Immunology Laboratory, AKiL, Center for Life Sciences and Technology Research, Bogazici University, Istanbul, Turkey.
authors.forename: Yetiş
authors.initials: Y
authors.lastname: Gültekin
authors.forename: Elif
authors.initials: E
authors.lastname: Eren
authors.forename: Nesrin
authors.initials: N
authors.lastname: Özören
mesh_terms: D000893:Anti-Inflammatory Agents / Q000276:immunology*; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology; D020169:Caspases / Q000235:genetics / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology; D003600:Cytosol / Q000276:immunology; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D019169:Jurkat Cells; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
chemical_list: D000893:Anti-Inflammatory Agents; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C508585:IL1B protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C503285:NLRC3 protein, human; C453881:NLRP3 protein, human; C402202:PYCARD protein, human; C099217:CASP5 protein, human; D020169:Caspases; D020170:Caspase 1