Expression of Syk in non-small cell lung cancer and its relationship with clinicopathological parameters

This study aims to research the expression of spleen tyrosine kinase(Syk)in non-small cell lung cancer(NSCLC)and the relationship between Syk and clinico-pathologic factors and p53.Immunohistochemistry was applied to detect the expression of Syk and p53 protein in 39 cases of NSCLC(23 cases of lung squamous cell can-cer,16 cases of lung adenocarcinoma)and tumor-sur-rounding normal lung tissues.The positive rate of Syk was 46.15%(18/39)and 100%(39/39)in NSCLC and tumor-surrounding normal lung tissues,respectively.The expres-sion level of Syk in NSCLC was significantly lower than that in tumor-surrounding normal lung tissues(P=0.000).The Syk expression was positively correlated with the p53 expression in NSCLC specimens(P=0.025).There was no significant association between Syk expression and lymph node metastasis,differentiation degree,tumor size and tumor node metastasis(TNM).The present study demonstrated that Syk was aberrantly expressed in the NSCLC and might have a significant impact on tumor growth and progression.

Caspase-1 activation by NLRP3 inflammasome dampens IL-33-dependent house dust mite-induced allergic lung inflammation

The cysteine protease caspase-1(Casp-1)contributes to innate immunity through the assembly of NLRP3,NLRC4,AIM2,and NLRP6 inflammasomes.Here we ask whether caspase-1 activation plays a regulatory role in house dust mite(HDM)-induced experimental allergic airway inflammation.We report enhanced airway inflammation in caspase-1-deficient mice exposed toHDMwith a marked eosinophil recruitment,increased expression of IL-4,IL-5,IL-13,aswell as full-length and bioactive IL-33.Furthermore,mice deficient for NLRP3 failed to control eosinophil influx in the airways and displayed augmented Th2 cytokine and chemokine levels,suggesting that the NLPR3 inflammasome complex controls HDM-induced inflammation.IL-33 neutralization by administration of soluble ST2 receptor inhibited the enhanced allergic inflammation,while administration of recombinant IL-33 during challenge phase enhanced allergic inflammation in caspase-1-deficient mice.Therefore,we show that caspase-1,NLRP3,and ASC,but not NLRC4,contribute to the upregulation of allergic lung inflammation.Moreover,we cannot exclude an effect of caspase-11,because caspase-1-deficient mice are deficient for both caspases.Mechanistically,absence of caspase-1 is associated with increased expression of IL-33,uric acid,and spleen tyrosine kinase(Syk)production.This study highlights acritical role of caspase-1 activation andNLPR3/ASCinflammasomecomplex in the down-modulation of IL-33 in vivo and in vitro,thereby regulating Th2 response in HDM-induced allergic lung inflammation.