Cooperation between fatty acid binding protein 5 and peroxisome proliferator-activated receptor ? in regulating macrophage programming

Abstract

<b>Background:</b> The resolution of inflammation is an active process that is tightly regulated. In its absence, tissues, like the lungs from COPD patients with recurrent exacerbations, become chronically inflamed. Over the course of inflammation, macrophage programming and function transition from inflammatory to pro-resolving. This process is known to involve the nuclear receptor Peroxisome Proliferator-Activated Receptor γ (PPARγ). In our previous work, we showed an interesting association between Fatty Acid Binding Protein 5 (FABP5) expression and PPARγ activity. In the current study we interrogated the role of FABP5 in macrophage programming. <b>Results:</b> Here, we demonstrate that FABP5 is necessary to initiate PPARγ activation and macrophage pro-resolving programming. We use the RNAscope tool in combination with co-immunofluorescence, immunoprecipitation, PPARγ activity assay, and chromatin immunoprecipitation to show that FABP5 and PPARγ not only interact but also regulate one another. By integrating flow cytometry, ELISA and the Seahorse technology, we extend our findings to illustrate that lack of FABP5 expression promotes pro-inflammatory macrophage programming. <b>Conclusions:</b> Taken together, these data provide evidence that FABP5 and PPARγ reciprocally regulate each other’s expression and function, consistent with a positive feedback regulatory loop between FABP5 and PPARγ to promote macrophage pro-resolving programming.