Lipin-1 contributes to IL-4 mediated macrophage polarization

Abstract

Macrophage responses contribute to a diverse array of pathologies ranging from infectious disease to sterile inflammation. Polarization of macrophages determines their cellular function within biological processes. Lipin-1 is a phosphatidic acid phosphatase in which its enzymatic activity contributes to macrophage pro-inflammatory responses. Lipin-1 also possesses transcriptional co-regulator activity and whether this activity is required for macrophage polarization is unknown. Using mice that lack only lipin-1 enzymatic activity or both enzymatic and transcriptional coregulator activities from myeloid cells, we investigated the contribution of lipin-1 transcriptional co-regulator function towards macrophage wound healing polarization. Macrophages lacking both lipin-1 activities did elicit IL-4 mediated gene expression to levels seen in either wild-type or lipin-1 enzymatically deficient macrophages. Furthermore, we provide evidence that the lack of myeloid-associated lipin-1 transcriptional co-regulator activity leads to impaired full thickness excisional wound healing. Our study demonstrates that lipin-1 transcriptional co-regulatory activity contributes to macrophage polarization and the macrophage contribution to wound healing in vivo.