Background: The lung macrophages govern the resolution phases of ALI/ARDS. Upon stimulation, resting macrophages are polarized into M1, utilizing glycolysis mainly, and M2, using fatty acid oxidation (FAO) mainly. Carnitine palmitoyltransferase1A (CPT1A) is a rate-limiting enzyme in FAO. Interleukin-10 (IL10) could inhibit LPS-induced glycolysis.

Aims and objectives?We assume that CPT1A and its regulated FAO is involved in the regulation of macrophage polarization, which could be positive regulated by IL10.

Methods: After nasal inhalation exogenous IL10 and/or LPS for 24h, wild type (WT), IL10^-/- and CPT1A^lyz2-/- mice were sacrificed. Murine bone marrow-derived macrophages (BMDMs) were extracted. The rt-PCR, Western-blot were used to test macrophage polarization, inflammation and mitochondrial damage. Seahorse XF96 and FAO metabolite related kit were used to test the level of glycolysis and FAO.

Results: We found that mice lacking IL10 and CPT1A produced an aggravate inflammatory response to LPS stimulation, which could be alleviated by exogenous IL10. The IL10 content of macrophages decreased in the lung tissue of CPT1A^lyz2-/- mice after LPS stimulation. We found IL10^-/- BMDMs became more glycolytic but less ?FAO? compared with WT BMDMs. However, the supplementation of IL10 into CPT1A^lyz2-/- macrophages showed a slight increase in the FAO level and a mild decrease in the glycolysis level. Our results provided strong evidence that CPT1A was capable of driving the polarization of BMDMs from M1 toward M2 phenotype ex vivo.

Conclusions: Our study reveals a role of IL10 in controlling macrophage polarization via positive regulated CPT1A associated FAO.