title: Small heterodimer partner interacts with NLRP3 and negatively regulates activation of the NLRP3 inflammasome.
abstract: Excessive activation of the NLRP3 inflammasome results in damaging inflammation, yet the regulators of this process remain poorly defined. Herein, we show that the orphan nuclear receptor small heterodimer partner (SHP) is a negative regulator of NLRP3 inflammasome activation. NLRP3 inflammasome activation leads to an interaction between SHP and NLRP3, proteins that are both recruited to mitochondria. Overexpression of SHP competitively inhibits binding of NLRP3 to apoptosis-associated speck-like protein containing a CARD (ASC). SHP deficiency results in increased secretion of proinflammatory cytokines IL-1β and IL-18, and excessive pathologic responses typically observed in mouse models of kidney tubular necrosis and peritoneal gout. Notably, the loss of SHP results in accumulation of damaged mitochondria and a sustained interaction between NLRP3 and ASC in the endoplasmic reticulum. These data are suggestive of a role for SHP in controlling NLRP3 inflammasome activation through a mechanism involving interaction with NLRP3 and maintenance of mitochondrial homeostasis.
authors: 1] Department of Microbiology, Chungnam National University School of Medicine, Daejeon 301-747, South Korea [2] Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, South Korea [3] Department of Molecular and Life Science, College of Science and Technology, Hanyang University, Ansan 426-791, South Korea.
authors: Chul-Su
authors: CS
authors: Yang
authors: 1] Department of Microbiology, Chungnam National University School of Medicine, Daejeon 301-747, South Korea [2] Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, South Korea [3] Department of Anatomy, College of Medicine, Konyang University, Daejeon 302-718, South Korea.
authors: Jwa-Jin
authors: JJ
authors: Kim
authors: 1] Department of Microbiology, Chungnam National University School of Medicine, Daejeon 301-747, South Korea [2] Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, South Korea.
authors: Tae Sung
authors: TS
authors: Kim
authors: Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea.
authors: Phil Young
authors: PY
authors: Lee
authors: 1] Department of Microbiology, Chungnam National University School of Medicine, Daejeon 301-747, South Korea [2] Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, South Korea.
authors: Soo Yeon
authors: SY
authors: Kim
authors: 1] Department of Microbiology, Chungnam National University School of Medicine, Daejeon 301-747, South Korea [2] Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, South Korea.
authors: Hye-Mi
authors: HM
authors: Lee
authors: 1] Department of Microbiology, Chungnam National University School of Medicine, Daejeon 301-747, South Korea [2] Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, South Korea.
authors: Dong-Min
authors: DM
authors: Shin
authors: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea.
authors: Loi T
authors: LT
authors: Nguyen
authors: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea.
authors: Moo-Seung
authors: MS
authors: Lee
authors: 1] Department of Microbiology, Chungnam National University School of Medicine, Daejeon 301-747, South Korea [2] Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, South Korea.
authors: Hyo Sun
authors: HS
authors: Jin
authors: Department of Biology, College of Life Science, Daejeon University, Daejeon 300-716, South Korea.
authors: Kwang-Kyu
authors: KK
authors: Kim
authors: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea.
authors: Chul-Ho
authors: CH
authors: Lee
authors: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea.
authors: Myung Hee
authors: MH
authors: Kim
authors: Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea.
authors: Sung Goo
authors: SG
authors: Park
authors: 1] Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, South Korea [2].
authors: Jin-Man
authors: JM
authors: Kim
authors: National Creative Research Initiatives Center for Nuclear Receptor Signals and Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, South Korea.
authors: Hueng-Sik
authors: HS
authors: Choi
authors: 1] Department of Microbiology, Chungnam National University School of Medicine, Daejeon 301-747, South Korea [2] Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon 301-747, South Korea.
authors: Eun-Kyeong
authors: EK
authors: Jo
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004789:Enzyme Activation; D057809:HEK293 Cells; D006706:Homeostasis; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011485:Protein Binding; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C492716:Nlrp3 protein, mouse; C498534:Pycard protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2; D020170:Caspase 1
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