Chondroitinase ABC treatment induces macrophage polarisation to anti-inflammatory state in central nervous system

Abstract

The microenvironment of the injured spinal cord activates macrophages/microglia to acquire pro-inflammatory M1 polarization with but transient and few acquiring anti-inflammatory M2 polarization. Following chondroitinase ABC (ChABC) treatment of the injured cord in a rat model, we however found lowered proportion of pro-inflammatory macrophages/microglia. We therefore hypothesized that chondroitin sulfate proteoglycans upregulated in the injured environment influences the balance between M1 and M2 polarization states. To test this, bone marrow collected from adult rats were subjected to in vitro derivation of macrophages and then stimulated with lipopolysaccharide to foster polarisation to the pro-inflammatory state. Following acute treatment of the cultures with ChABC versus vehicle control, RT-PCR analysis for transcripts of polarization markers found lowered expression of such M1 markers as inducible nitric oxide synthase and CD86. In contrast, expression such M2 markers as arginase-1, CCL22 and IL10 were found to be elevated. Experiments with the acutely injured rat model revealed the ChABC-treated injured cord environment increased levels of the IL10 and transforming growth factors beta (TGF-beta) transcripts as compared to the vehicle control. The results add impetus to the development of strategies for timely shift to M2 polarization as a therapeutic goal.