Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of gout is relatively high worldwide, and many gout patients suffer from uric acid nephropathy (UAN) concomitantly. ELR-CXC chemokines such as CXCL8 and CXCL1 have a elevated expression in UAN. In this research, a mouse UAN model was established for a 12 week duration, and uric acid-related crystals were observed. CXCL8(3-72)K11R/G31P (G31P) is a mutant protein of CXCL8/interleukin 8 (IL-8), which has been reported to have therapeutic efficacy in both inflammatory diseases and malignancies for it acts as a selective antagonist towards CXCR1/CXCR2. In this study, G31P-treated mice showed declined production of the blood urea nitrogen (BUN) level and urine volume in UAN mice compared with G31P-untreated UAN counterparts. In addition, G31P effectively improved renal fibrosis, and reduced uric acid accumulation and leukocyte infiltration in UAN kidneys. Furthermore, the expressions of CXCL1 and CXCL2 were reduced and the activation of NOD-like receptors protein 3 (NLRP3) was inhibited by G31P treatment. This study has demonstrated that G31P attenuates inflammatory progression in chronic UAN, and plays a renoprotective function.
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PMID:CXCR1/CXCR2 antagonist G31P inhibits nephritis in a mouse model of uric acid nephropathy. 3025 27

Neutrophils are crucial in the process of gout flare and remission. The signal transduction pathway of chemokine plays a vital role in the chemotaxis and activation of neutrophils. CXCR2 gene knocked out can avoid the acute neutrophilic inflammation stimulated by monosodium urate (MSU) crystals in mice. To investigate the relationship among CXCR1 rs2234671, CXCR2 rs1126579, and rs2230054 polymorphisms with gout arthritis flare in the Chinese Han male population, a case-control study was carried out in 412 gout patients and 508 gout-free individuals. TaqMan probes fluorescence real-time polymerase chain reaction (PCR) was used to genotype CXCR1 rs2234671, CXCR2 rs1126579, and rs2230054 SNPs. There was a clear link between CXCR2 rs2230054 T included genotypic and T allelic frequencies and gout cases (c2 = 9.286, p = 0.002 by genotype, c2 = 8.639, p = 0.003 by allele), while no significant differences were observed between the gouty arthritis group and the control group in CXCR1 rs2234671 and CXCR2 rs1126579 genotypic and allelic frequencies. Multivariate logistic regression analysis showed that the T genotype included in rs2230054 can decrease the risk of gouty arthritis (adjusted OR = 0.47; 95% CI: 0.31-0.74) compared with the CC genotype. Our study might suggest that rs2230054 in CXCR2 is associated with susceptibility to gout in Chinese males.
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PMID:Genetic association of polymorphism rs2230054 in CXCR2 gene with gout in Chinese Han male population. 3242 84