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