The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
-
A subset of asthma patients suffer from glucocorticoid (GC) insensitivity. T-helper cell type 17 cells have an emerging role in GC insensitivity, although the mechanisms are still poorly understood. We investigated whether interleukin (IL)-17A induces GC insensitivity in airway epithelium by studying its effects on responsiveness of tumour necrosis factor (TNF)-α-induced IL-8 production to budesonide in human bronchial epithelial 16HBE cells. ⋯ In contrast, IL-17A did not affect budesonide-induced transcriptional activity of the GC receptor, suggesting that IL-17A does not impair the actions of the ligated GC receptor. In conclusion, we have shown for the first time that IL-17A induces GC insensitivity in airway epithelium, which is probably mediated by PI3K activation and subsequent reduction of HDAC2 activity. Thus, blockade of IL-17A or downstream signalling molecule PI3K may offer new strategies for therapeutic intervention in GC-insensitive asthma.
-
The aim of our study was to investigate the association between rapid weight gain in the first 3 months of life and the prevalence of wheeze in the first years of life and lung function at 5 yrs of age. The infants selected were participating in an ongoing birth cohort. Information on growth and respiratory symptoms was collected during the first year of life, and on primary care consultations during total follow-up. ⋯ FEV(1) and FEF(25-75%) were reduced by 34 mL (adjusted regression coefficient -0.034, 95% CI -0.056- -0.013; p=0.002) and 82 mL (adjusted regression coefficient -0.082, 95% CI -0.140- -0.024; p=0.006) per every one-point z-score increase in weight gain, respectively. These associations were independent of birthweight. Rapid early weight gain is a risk factor for clinically relevant wheezing illnesses in the first years of life and lower lung function in childhood.