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Cytokine and chemokine modification by Toll-like receptor polymorphisms is associated with nasopharyngeal carcinoma.

ABSTRACT: Toll-like receptors (TLR) play a pivotal role in sensing a wide range of pathogens, including bacteria, fungi and viruses. A dysregulation of TLR signaling may increase the risk of developing chronic inflammatory diseases and cancers. The aim of this study was to investigate the association of TLR2 R753Q, TLR4 D299G, and T399I polymorphisms with nasopharyngeal carcinoma (NPC) and to explore the effects of these polymorphisms on cytokine and chemokine expression in NPC biopsies. The genotypes of the three loci among 236 patients with NPC and 287 healthy controls were determined by PCR-RFLP. Cytokines and chemokines mRNA and protein in NPC biopsies were measured by real-time quantitative PCR and ELISA, respectively. Results showed that the combined CT/TT genotype of T399I was associated with increased NPC risk, with an odds ratio of 1.853 (95% confidence interval: 1.184-2.961). Also, individuals with the T allele of T399I showed a 1.842-fold increase in NPC risk compared to those with the T399I C allele (95% confidence interval: 1.213-3.015). Messenger RNA levels of interleukin (IL)-1?, tumor necrosis factor-? and IL-10 were significantly elevated in patients with T399I combined CT/TT genotype; IL-1? and IL-10 protein concentration significantly increased in NPC patients with T399I combined CT/TT genotype compared to those with the T399I CC genotype. Our data suggest that TLR4 T399I modify cytokines and chemokines patterns and play a role in the development of NPC.

SUBMITTER: Yang ZH

PROVIDER: S-EPMC7659248 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Cytokine and chemokine modification by Toll-like receptor polymorphisms is associated with nasopharyngeal carcinoma.

Yang Zhi-Hui ZH Dai Qiong Q Gu Ying-Jiang YJ Guo Qing-Xi QX Gong Li L

Cancer science 20120214 4

Toll-like receptors (TLR) play a pivotal role in sensing a wide range of pathogens, including bacteria, fungi and viruses. A dysregulation of TLR signaling may increase the risk of developing chronic inflammatory diseases and cancers. The aim of this study was to investigate the association of TLR2 R753Q, TLR4 D299G, and T399I polymorphisms with nasopharyngeal carcinoma (NPC) and to explore the effects of these polymorphisms on cytokine and chemokine expression in NPC biopsies. The genotypes of ...[more]

PMID: 22320262

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Project description:ContextAltered cytokine levels and chronic low-grade inflammation contribute to metabolic dysfunction in obesity. The extent of cytokine changes and their impact on metabolic improvements after bariatric surgery have not been fully explored.ObjectiveTo compare 76 circulating cytokines, chemokines, and secreted cytokine receptors in subjects with obesity and lean subjects and determine how these cytokines are altered by bariatric surgery.Design, setting, and participantsA total of 37 patients with obesity and 37 lean patients in a cross-sectional study at an academic medical center. We also investigated cytokine changes in 25 patients with obesity after bariatric surgery.InterventionBariatric surgery (Roux-en-Y gastric bypass and vertical sleeve gastrectomy).Main outcome measuresQuantification of 76 circulating cytokines, chemokines, and secreted cytokine receptors.ResultsA total of 13 cytokines were significantly higher, and 4 lower, in patients with obesity relative to lean controls. Soluble vascular endothelial growth factor receptor 2 (sVEGFR2), soluble TNF receptor (sTNFR) 1, and sTNFR2 were positively correlated, and soluble receptor for advanced glycation end-products was inversely correlated, with weight and body mass index. sTNFR2 was positively correlated with fasting glucose, homeostatic model assessment of insulin resistance, and hemoglobin A1c. After bariatric surgery, adiponectin increased, and leptin decreased. Elevated sVEGFR2 levels in patients with obesity were decreased (P = 0.01), whereas reduced chemokine (C-X-C motif) ligand (CXCL) 12 levels in patients with obesity increased (P = 0.03) after surgery. Patients with higher soluble interleukin receptor (sIL) 1R2 and sIL-6R levels before surgery had greater weight loss after surgery (P < 0.05).ConclusionsWe demonstrate that chemokine (C-C motif) ligand (CCL) 14, sVEGFR2, and platelet-derived growth factor BB are elevated in obesity, and CXCL12, CCL11, and CCL27 are lower in obesity. We found clinically concordant directionality between lean and patients with obesity and before vs after surgery for six cytokines, suggesting that bariatric surgery shifted the cytokine profiles of patients with obesity toward that of lean controls.

Dataset Information

Cytokine and chemokine modification by Toll-like receptor polymorphisms is associated with nasopharyngeal carcinoma.

Publications

Cytokine and chemokine modification by Toll-like receptor polymorphisms is associated with nasopharyngeal carcinoma.

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