Human IL-19 ELISA Kit

Asthma is a chronic inflammatory disease of the airway. Its major symptoms are reversible breathing problems causing airway narrowing and obstruction. IL-19 is a member of the IL-10 family cytokines. We previously showed that IL-19 induces T-helper 2 (Th2) cytokines and that asthma patients had higher serum IL-19 levels. To further examine whether inhibiting IL-19 and its receptor (IL-20R1) protected rodents against asthma, we used Dermatophagoides pteronyssinus (Der p; house dust mites) to induce chronic airway inflammation in wild-type C57BU6 and IL-20R1-deficient mice and then analyzed the effect of the IL-20R1 deficiency on the pathogenesis of asthma. We also examined whether inhibiting IL-19 and IL-20R1 ameliorated Der p-induced chronic asthma. Der p induced IL-19 in lung airway epithelial cells, type 2 alveolar cells, and alveolar macrophages. An IL-20R1 deficiency abolished IL-19-induced Th2 cell differentiation in vitro. Th2 cytokine expression, immune cell infiltration in the bronchoalveolar lavage, airway hyperresponsiveness (AHR), and bronchial wall thickening were lower in Der p-challenged IL-20R1-deficient mice. Anti-IL-20R1 monoclonal antibody (mAb) 51D and IL-19 polyclonal antibody (pAb) both ameliorated Der p-induced AHR, lung immune cell infiltration, bronchial wall thickening, and Th2 cytokine expression. Moreover, we confirmed that anti-IL-19 mAb (1BB1) attenuated lung inflammation in a rat ovalbumin-induced asthma model. This is the first report to show that inhibition of IL19 by targeting IL-19 or IL-20R1 protected rodents from allergic lung inflammation. Our study suggests that targeting IL-19 signaling might be a novel therapeutic strategy for treating allergic asthma.

Background: Recent genetic association studies identified more than 160 susceptibility loci for inflammatory bowel disease in Caucasian populations, but studies in Asian populations are limited. We have previously reported 3 loci associated with Korean ulcerative colitis (UC). Methods: Using the Immunochip custom single nucleotide polymorphisms (SNP) array designed for dense genotyping of 186 known disease loci from 12 immune-mediated diseases, we analyzed 705 patients with UC and 1178 controls for 536,821 SNPs (89,057 genotyped and 447,764 imputed) in the discovery stage followed by replication in additional 980 affected individuals and 2694 controls in a Korean population. Results: We confirmed the associations of 10 known UC risk loci in Koreans: rs76418789 in IL23R (combined P = 1.25 x 10(-8)), rs4728142 in IRF5 (combined P = 3.17 x 10(-8)), rs1830610 near JAK2 (combined P = 2.28 x 10(-9)), rs1555791 near TNFRSF14 (combined P = 1.62 x 10(-6)), rs880790 between IL10-IL19 (combined P = 3.73 x 10(-6)), rs10185424 between IL1R2-IL1R1 (combined P = 1.54 x 10(-4)), rs6478108 in TNFSF15 (combined P = 9.28 x 10(-5)), rs861857 between UBE2L3-YDJC (combined P = 3.05 x 10(-5)), rs1801274 in FCGR2A (discovery P = 1.54 x 10(-4)), and rs17085007 between GPR12-USP12 (discovery P = 3.64 x 10(-4)). The percentage of phenotype variance explained by the 13 risk loci (including 3 previously reported loci) was 5.61% in Koreans (on the liability scale, population prevalence = 0.0308%). Conclusions: Our study increased the number of UC susceptibility loci in Koreans to 13 and highlighted the extensive sharing of genetic risk across populations of UC.