Butyrate regulation of distinct macrophage subsets: Opposing effects on M1 and M2 macrophages

Abstract

Mucosal tolerance is central to efficient gastrointestinal tract function, tolerating food and commensal bacteria, whilst maintaining immune responsiveness to pathogens. Mucosal macrophages play a pivotal role in tolerance; whereas in inflammatory bowel disease, dysfunctional macrophages lead to tolerance breakdown, whereby commensals perpetuate inflammation. Macrophage subsets however, determine effector function: M1s are pro-inflammatory whereas M2s are antiinflammatory/regulatory. In addition to commensal bacteria, butyrate, a short chain fatty acid probiotic metabolite, may also modulate macrophage-mediated tolerance. The human monocytic cell line, THP-1, was used to investigate butyrate immunoregulation in M1 and M2 macrophages, generated by monocyte differentiation in the presence of PMA or vitamin D3 respectively. Butyrate modulation of LPS- and PGN-induced TNFα, IL-1β, IL-10 and NFkB was measured by sandwich ELISA and reporter gene assay, respectively. Data indicated butyrate suppresses LPS- and PGN-induced monocyte and M2 production of IL-1β and TNFα, M1-induced TNFa and IL-10 but failed to modulate Ml-induced IL-1β. Additionally, butyrate augmented M2 IL-10 production, LPS- and PGN-stimulatedMl and LPS-inducedM2 NFkB activity but failed to regulate PGN-induced M2 NF-kB. In conclusion, butyrate differentially regulates macrophage cytokine production and NFkB activation, which is subsetdependent and suggestive of a cautionary approach to butyrate use in treatment of mucosal inflammation. Copyright © 2011 by New Century Health Publishers, LLC