A potential role of the proteoglycan biglycan in a murine model of allergic airway inflammation

Background: The extracellular matrix component biglycan (Bgn), a small leucine-rich proteoglycan (SLRP), is known to act as damage-associated pattern (DAMP). Following secretion by activated macrophages or proteolytic digestion the soluble biglycan is capable of binding to TLR2, TLR4 and P2X7 thereby triggering downstream signalling events leading to an increased production of pro-inflammatory cytokines like IL-1ß, TNF-alpha as well as the chemotractant CXCL13.

Purpose: Due to its role in inflammation we suggested that Bgn deficiency influences the development of allergen-induced asthma.

Method: Bgn^-/- and Bgn^+/+ mice (C57Bl/6) were sensitized with ovalbumin-alum (OVA-alum) and challenged with OVA-aerosols for 3 days.

Results: After OVA challenge Bgn deficient mice showed less inflammatory cells in the bronchoalveolar lavage fluid and lung tissue sections accompanied by decreased Th2 cytokine production in the mediastinal lymphnodes compared to Bgn^+/+ mice. Further more Bgn deficient dendritic cells showed a limited priming capacity of Th2 immunity in vitro as well as in a DC driven model of allergic airway inflammation in vivo.

Conclusion: Our findings show biglycan is involved in regulation of allergic airway inflammation, suggesting that targeting Bgn and/or the corresponding receptors might be a potential therapeutic target for treatment of asthma.