Soluble biglycan promotes ovalbumin induced airway inflammation by modulating dendritic cell function in mice

Abstract

Background: The small leucine-rich proteoglycan biglycan (Bgn) is a component of the extracellular matrix and capable of facilitating inflammatory processes. Following secretion by activated macrophages or proteolytic digestion the soluble biglycan induces TLR2, TLR4 as well as P2RX7 mediated signalling resulting in an increased production of pro-inflammatory cytokines. Although biglycan has been implicated in the pathogenesis of various diseases including contact dermatitis its role in allergen-induced airway inflammation (AAI) remains unclear. Methods: Bgn-deficient mice were applied to an acute ovalbumin (OVA) driven model of AAI. In addition, OVA-primed bone marrow derived dendritic cells (BMDCs) were adoptively transferred into either wild type or Bgn-deficient animals before OVA challenge. After the final OVA aerosol exposure the hallmarks of the acute airway inflammation were characterised. Results: Bgn-deficiency in mice is accompanied by an attenuated AAI pathogenesis in terms of BALF eosinophilia, bronchial hyper-responsiveness, peribronchial inflammation and Th2 cytokine production of OVA re-stimulated mediastinal lymph node cells compared to wild type mice. Furthermore, Bgn-deficient OVA-primed BMDCs induced an alleviated airway inflammation after adoptive transfer into wild type mice. However, wild type OVA-primed BMDCs failed to completely restore the airway inflammation after being adoptively transferred into Bgn-deficient animals. Conclusion: Biglycan promotes OVA induced airway inflammation in mice by modulating dendritic cell function.