Autophagy and genetic predisposition have been suggested to potentially play roles in the development of asthma. However, little is known about the role of autophagy in the pathogenesis of severe asthma.

Background  Urticaria is the commonest cutaneous reaction caused by aspirin or other nonsteroidal anti‐inflammatory drugs. The pathogenesis of aspirin‐induced urticaria (AIU) is not fully understood, but appears to involve mast cell activation and neutrophil infiltration.

BACKGROUND:It has been known that interleukin (IL)-10 promoter polymorphisms at -1082A/G, -819T/C and -592A/C, may influence IL-10 expression and associate with asthma. Interleukin-10 facilitates the regulatory function of transforming growth factor (TGF)-beta. The goal of this study was to investigate a gene-gene interaction between IL-10 and TGF-beta1 polymorphisms in Korean asthmatics with aspirin hypersensitivity.METHODS:Single-nucleotide polymorphism genotyping of IL-10 and TGF-beta1 genes was performed and the functional effect of the IL-10 polymorphisms was analysed applying a luciferase reporter assay and an electrophoretic mobility shift assay.RESULTS:Among the patients with asthma, polymorphism at -1082A/G was significantly associated with the phenotype of aspirin-intolerant asthma, AIA (P = 0.007, P(c) = 0.021). Moreover, a synergistic effect between the TGF-beta1-509C/T and IL-10-1082A/G polymorphisms on the phenotype of AIA was noted; when stratified by the presence of rhinosinusitis, the frequency of rare alleles (the CT or TT genotype of TGF-beta1-509C/T and AG or GG genotype of IL-10-1082A/G) was significantly higher in the patients with AIA (15.2%) when compared with those with ATA (6.3%, P = 0.031; odds ratio 4.111; 95% confidence interval 1.504-11.235). In an in vitro functional assay, the -1082G reporter plasmid exhibited significantly greater promoter activity when compared with the -1082A construct in Jurkat T cells (P = 0.011). Moreover, we found that the transcription factor Myc-associated zinc-finger protein preferentially bound the -1082G allele.CONCLUSION:Our results suggest that IL-10 promoter polymorphisms contribute to the development of AIA and that rhinosinusitis may interact genetically with TGF-beta1.

Summary Background Toluene diisocyanate (TDI) is the most important cause of occupational asthma, but the genetic mechanism of TDI‐induced asthma is still unknown. Objective The objective of the study was to identify susceptibility alleles associated with the TDI‐induced asthma phenotype. Methods We conducted a genome‐wide association study in 84 patients with TDI‐induced asthma and 263 unexposed healthy normal controls using Affymetrix 500K SNPchip. We also investigated the relationships between genetic polymorphisms and transcript levels in Epstein–Barr virus‐transformed lymphoblastoid cell lines from patients with TDI‐induced asthma enrolled in this study. Results Genetic polymorphisms of CTNNA3 (catenin alpha 3, alpha‐T catenin) were significantly associated with the TDI‐induced asthma phenotype (5.84 × 10 −6 for rs10762058, 1.41 × 10 −5 for rs7088181, 2.03 × 10 −5 for rs4378283). Carriers with the minor haplotype, HT2 [GG], of two genetic polymorphisms (rs10762058 and rs7088181) showed significantly lower PC 20 methacholine level ( P =0.041) and lower mRNA expression of CTNNA3 than non‐carriers ( P =0.040). A genetic polymorphism in the 3′ downstream region of CTNNA3 (rs1786929), as identified by DNA direct sequencing, was significantly associated with the TDI‐induced asthma phenotype ( P =0.015 in recessive analysis model) and the prevalence of serum‐specific IgG to cytokeratin 19 ( P =0.031). Conclusion These findings suggested that multiple genetic polymorphisms of CTNNA3 may be determinants of susceptibility to TDI‐induced asthma.

We previously reported that a methanolic extract of Coptis japonica, which is a well-known traditional oriental medicine, inhibits morphine-induced conditioned place preference (CPP) in mice. Berberine is a major component of Coptis japonica extract, and it has been established that the adverse effects of morphine on the brain involve dopamine (DA) receptors. However, to our knowledge, no study has investigated the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance in mice. Here, we investigated the effects of berberine on morphine-induced locomotor sensitization and on the development of analgesic tolerance. Furthermore, we examined the effects of berberine treatment on N-methyl-d-aspartate (NMDA) receptor channel activity expressed in Xenopus laevis oocytes. Berberine was found to completely block both morphine-induced locomotor sensitization and analgesic tolerance, and reduce D1 and NMDA receptor bindings in the cortex. Moreover, berberine markedly inhibited NMDA current in Xenopus laevis oocytes expressing NMDA receptor subunits. Our results suggest that the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance are closely related to the modulation of D1 and NMDA receptors, and that berberine should be viewed as a potential novel means of attenuating morphine-induced sensitization and analgesic tolerance.