METHODS: All deoxyribonucleic acid (DNA) samples were genotyped for TNFα-1031 and TNFβ+252 genes by mean of polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP). The statistical analysis were carried out using chi-square test or Fisher exact test to determine the associations of these gene polymorphisms in CRS. Multiple logistic regression was performed to evaluate the associations of these gene polymorphisms in CRS and its related risk factors.
RESULTS: The genotype and allele frequencies of TNFα-1031 and TNFβ+252 gene did not show any significant associations between CRS and healthy controls. However, a significantly statistical difference of TNFα-1031 was observed in CRS participants with atopy (P-value, 0.045; odds ratio, 3.66) but not in CRS with asthma or aspirin intolerance.
CONCLUSION: Although the presence of TNFα-1031 and TNFβ+252 gene polymorphisms did not render any significant associations between CRS and healthy control, this study suggests that TNFα-1031 gene polymorphisms in CRS patients with atopy may be associated with increase susceptibility towards CRS.
METHODS AND RESULTS: Transverse aortic constriction (TAC)/sham surgery were carried out in both IL-33 and WT-littermates. Echocardiographic measurements were performed at frequent interval during the study period. Heart was harvested for RNA and histological measurements. Following mechanical overload by TAC, myocardial mRNA expressions of Th1 cytokines, such as TNF-α were enhanced in IL-33(-/-) mice than in WT mice. After 8-weeks, IL-33(-/-) mice exhibited exacerbated left ventricular hypertrophy, increased chamber dilation, reduced fractional shortening, aggravated fibrosis, inflammation, and impaired survival compared with WT littermates. Accordingly, myocardial mRNA expressions of hypertrophic (c-Myc/BNP) molecular markers were also significantly enhanced in IL-33(-/-) mice than those in WT mice.
CONCLUSIONS: We report for the first time that ablation of IL-33 directly and significantly leads to exacerbate cardiac remodeling with impaired cardiac function and survival upon mechanical stress. These data highlight the cardioprotective role of IL-33/ST2 system in the stressed myocardium and reveal a potential therapeutic role for IL-33 in non-ischemic HF.