The role of AP2 on airway hyperresponsiveness and the formation of inflammatory response in asthma pathogenesis

Asthma is a heterogeneous disease characterized by chronic airway inflammation and bronchial hyperresponsiveness. Researches on the role of adipocyte-protein2, aP2, also known as FABP4 in asthma pathogenesis are limited. It's suggested that circulating-aP2 may play role in allergic-asthma pathogenesis. The mechanism by which it exerts its effect, and the source of aP2 that acts on airways is not fully understood. In this project, it's aimed to study the aP2's role in the development of allergic airway inflammation and hyperresponsiveness on experimental allergic-asthma-models developed in aP2f/fmice. In order to determine the source of aP2 in the pathogenesis of asthma, tissue-specific aP2-deficient experimental models were planned. For this purpose, OVA or HDM induced experimental allergic-asthma-models in aP2f/fmice were developed. Bronchoprovocation was performed with increasing concentrations of methacholine, no difference was observed in RN and Rrs values. Therefore tissue-specific-models were not studied. In-vitro studies were conducted on human-bronchial-epithelial-cells (BEAS-2B), mouse-lung-epithelial-cells (MLE-12), murine-alveolar-macrophages (MH-S) to evaluate the contribution of aP2-protein in airway inflammation. CCL2 ,IL-1B,TSLP gene expressions in BEAS-2B;CCL2 gene expression in MLE-12 and CCL2, IL-1B gene expressions in MH-S were increased by recombinant-aP2 treatment. CCL2-gene expression in BEAS-2B and MLE-12 cells, and IL-1B gene expression in BEAS-2B and MH-S were elevated significantly with aP2+OVA treatment when compared with OVA-group. aP2-gene expression was significantly increased in LPS-treated alveolar-macrophages. Interestingly aP2-gene expression as well as aP2protein were not detected in epithelial-cell-culture. Preliminary data have shown that aP2 might trigger the production of proinflammatory cytokines and chemokines, and may potentiate the inflammatory-response due to allergen exposure.