Interleukin-1α Is a Critical Mediator of the Response of Human Bronchial Fibroblasts to Eosinophilic Inflammation
Ksenija Bernau,
Jonathan P. Leet,
Heather Floerke,
Ellen M. Bruhn,
Andrea L. Noll,
Ivy S. McDermott,
Stephane Esnault,
Nizar N. Jarjour,
Nathan Sandbo
Affiliations
Ksenija Bernau
Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
Jonathan P. Leet
Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
Heather Floerke
Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
Ellen M. Bruhn
Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
Andrea L. Noll
Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
Ivy S. McDermott
Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
Stephane Esnault
Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
Nizar N. Jarjour
Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
Nathan Sandbo
Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
Eosinophils contribute to allergic inflammation in asthma in part via elaboration of a complex milieu of soluble mediators. Human bronchial fibroblasts (HBF) respond to stimulation by these mediators by acquiring a pro-inflammatory profile including induction of interleukin 6 (IL6) and IL8. This study sought to determine key component(s) of eosinophil soluble factors that mediate IL6 and IL8 induction in HBF. HBF treated with eosinophil-derived soluble mediators were analyzed for gene expression, intracellular signaling, and IL6 and IL8 secretion following inhibition of inflammatory signaling. Segmental allergen bronchoprovocation (SBP-Ag) was performed in mild asthmatics and bronchoalveolar lavage fluid was analyzed for eosinophils and cytokines. We found that signaling via the IL1α/IL1 receptor is an essential component of the response of HBF to eosinophil-derived soluble factors. IL1α-dependent activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling is required to induce IL6 secretion. However, NFκB signaling is dispensable for the induction of IL8, whereas Src is required. IL1α is associated with eosinophilic inflammation in human airways after SBP-Ag. Conclusions: IL1α appears to be a critical component of the soluble eosinophil-derived milieu that drives pro-inflammatory bronchial fibroblast responses and associates with eosinophilic inflammation following SBP-Ag. Disruption of IL1α-signaling could modify the downstream effects of eosinophilic inflammation on airway remodeling.
