title: P2X7R: a potential key regulator of acute gouty arthritis.
abstract: OBJECTIVE
  Acute gouty arthritis is an inflammatory disease resulting from the precipitation of long-term hyperuricemia-induced monosodium urate (MSU) crystals in joints, which stimulates the production of interleukin-1beta (IL-1β) and initiates an inflammatory reaction. However, some patients having MSU crystals in the joints never develop acute gouty arthritis, indicating that other predisposing factors are required for the disease onset. This review described the mechanism of production of IL-1β by MSU crystals and other possible factors during a gout attack.
  
  
  METHODS
  The relevant English literature on IL-1β secretion stimulated by MSU crystals and other possible factors during acute gouty arthritis flares was searched and carefully reviewed.
  
  
  RESULTS
  MSU crystals lead to the onset of acute gouty arthritis mainly through the activation of Toll-like receptors (TLRs) and NACHT-LRR-PYD-containing protein 3 (NALP3) inflammasome signaling and downstream IL-1β production. The predisposing factors of acute gouty arthritis, such as strenuous exercise, cold, alcolholism, and overeating have a common characteristic inducing dramatic changes of adenosine triphosphate (ATP) in the body. The ATP changes can activate the purinergic receptor P2X ligand-gated ion channel 7 (P2X7R) signaling system to regulate IL-1β secretion.
  
  
  CONCLUSIONS
  We hypothesize that acute gouty arthritis is induced by two synergistic effects; one is the stimulation of MSU crystals and the other is the activation of P2X7R signaling pathways by extracellular ATP changes, which together lead to the production of IL-1β and the initiation of acute gouty arthritis. This hypothesis will provide a new avenue for the prevention and treatment of acute gouty arthritis.
authors.affiliation: Department of Rheumatology and Immunology, Anhui Provincial Hospital, Affiliated to Anhui Medical University, No. 17 LuJiang Rd, Hefei 230001, China. Electronic address: taojinhui2010@yahoo.cn.
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Tao
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiang-Pei
authors.initials: XP
authors.lastname: Li
mesh_terms: D015210:Arthritis, Gouty / Q000378:metabolism*; D006801:Humans; D033461:Hyperuricemia / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D058486:Receptors, Purinergic P2X7
keywords: Acute gouty arthritis; Interleukin-1beta; Receptor, P2X7