The Role of Uric Acid as an Endogenous Danger Signal in Immunity and Inflammation

被引:188
作者
Ghaemi-Oskouie, Faranak [1 ,2 ]
Shi, Yan [1 ,2 ]
机构
[1] Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada
[2] Univ Calgary, Immunol Res Grp, Calgary, AB T2N 4N1, Canada
关键词
Uric acid; Monosodium urate; Inflammation; Adjuvanticity; NLRP3; IL-1; beta; TLR; Lipids;
D O I
10.1007/s11926-011-0162-1
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Gout is an ancient disease that still plagues us. Its pathogenic culprit, uric acid crystal deposition in tissues, is a strong inflammatory stimulant. In recent years, the mechanisms through which uric acid crystals promote inflammation have been a subject of increasing interest among rheumatologists and immunologists. Uric acid has been identified as an endogenous adjuvant that drives immune responses in the absence of microbial stimulation. Because uric acid is a ubiquitous metabolite that is produced in high quantities upon cellular injury, the ramifications of its effects may be considerable in health and in disease. Uric acid crystals also have been shown to trigger interleukin-1 beta-mediated inflammation via activation of the NOD-like receptor protein (NLRP)3 inflammasome, a multimolecular complex whose activation appears to be central to many pathological inflammatory conditions. In this article, we review the possible mechanisms of uric acid-mediated inflammation and offer some historical perspectives on what has been learned about the complex effects of a relatively simple substance.
引用
收藏
页码:160 / 166
页数:7
相关论文
共 45 条
[1]
Crystal-induced neutrophil activation VI.: Involvement of FcγRIIIB (CD16) and CD11b in response to inflammatory microcrystals [J].
Barabé, F ;
Gilbert, C ;
Liao, N ;
Bourgoin, SG ;
Naccache, PH .
FASEB JOURNAL, 1998, 12 (02) :209-220
[2]
Identification of a key pathway required for the sterile inflammatory response triggered by dying cells [J].
Chen, Chun-Jen ;
Kono, Hajime ;
Golenbock, Douglas ;
Reed, George ;
Akira, Shizuo ;
Rock, Kenneth L. .
NATURE MEDICINE, 2007, 13 (07) :851-856
[3]
MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals [J].
Chen, Chun-Jen ;
Shi, Yan ;
Hearn, Arron ;
Fitzgerald, Kate ;
Golenbock, Douglas ;
Reed, George ;
Akira, Shizuo ;
Rock, Kenneth L. .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (08) :2262-2271
[4]
FUNCTIONS OF LYSOSOMES [J].
DEDUVE, C ;
WATTIAUX, R .
ANNUAL REVIEW OF PHYSIOLOGY, 1966, 28 :435-+
[5]
Desaulniers P, 2001, J LEUKOCYTE BIOL, V70, P659
[6]
SOCIAL CLASS GRADIENT OF SERUM URIC ACID LEVELS IN MALES [J].
DUNN, JP ;
MAUSNER, J ;
BROOKS, GW ;
COBB, S ;
RODNAN, GP .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1963, 185 (06) :431-&
[7]
Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants [J].
Eisenbarth, Stephanie C. ;
Colegio, Oscar R. ;
O'Connor, William, Jr. ;
Sutterwala, Fayyaz S. ;
Flavell, Richard A. .
NATURE, 2008, 453 (7198) :1122-U13
[8]
Molecular identification of a renal urate-anion exchanger that regulates blood urate levels [J].
Enomoto, A ;
Kimura, H ;
Chairoungdua, A ;
Shigeta, Y ;
Jutabha, P ;
Cha, SH ;
Hosoyamada, M ;
Takeda, M ;
Sekine, T ;
Igarashi, T ;
Matsuo, H ;
Kikuchi, Y ;
Oda, T ;
Ichida, K ;
Hosoya, T ;
Shimokata, K ;
Niwa, T ;
Kanai, Y ;
Endou, H .
NATURE, 2002, 417 (6887) :447-452
[9]
Uric acid and cardiovascular risk [J].
Feig, Daniel I. ;
Kang, Duk-Hee ;
Johnson, Richard J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (17) :1811-1821
[10]
STUDIES OF URATE CRYSTALLIZATION IN RELATION TO GOUT [J].
FIDDIS, RW ;
VLACHOS, N ;
CALVERT, PD .
ANNALS OF THE RHEUMATIC DISEASES, 1983, 42 :12-15