Abstract
The nutritional curcumin (CUR) is beneficial in cell-mediated autoimmune diseases. The molecular mechanisms underlying this food-mediated silencing of inflammatory immune responses are poorly understood. By investigating antigen-specific immune responses we found that dietary CUR impairs the differentiation of Th1/Th17 cells in vivo during encephalomyelitis and instead promoted Th2 cells. In contrast, feeding CUR had no inhibitory effect on ovalbumin-induced airway inflammation. Mechanistically, we found that CUR induces an anti-inflammatory phenotype in dendritic cells (DC) with enhanced STAT3 phosphorylation and suppressed expression of Il12b and Il23a. On the molecular level CUR readily induced NRF2-sensitive heme oxygenase 1 (HO-1) mRNA and protein in LPS-activated DC. HO-1 enhanced STAT3 phosphorylation, which enriched to Il12b and Il23a loci and negatively regulated their transcription. These findings demonstrate the underlying mechanism through which a nutritional can interfere with the immune response. CUR silences IL-23/Th17-mediated pathology by enhancing HO-1/STAT3 interaction in DC.
Highlights
Silencing inflammatory pathways by nutritionals may have sustainable impact on treatment strategies for chronic immune-mediated diseases
The activation of STAT3 by CUR in dendritic cells (DC) is mediated through heme oxygenase 1 (HO1), a stress-response protein readily induced by CUR in vitro and in vivo
The nutritional CUR has been reported to improve the outcome of experimental autoimmune encephalomyelitis (EAE) in rodents[13,14,15,16] by using artificial and parenteral routes of administration
Summary
Silencing inflammatory pathways by nutritionals may have sustainable impact on treatment strategies for chronic immune-mediated diseases. Despite the direct role of nutritionals as allergens or inducers of oral tolerance, increasing data suggests that dietary factors or their metabolites can affect the nature of T cell-mediated immune responses[1]. This has been intensively studied for dietary fibre metabolites like short-chain fatty acids in experimental models of colitis[2] or allergic airway inflammation[3]. Other examples of nutritional compounds with anti-tumoral and anti-inflammatory activities are the natural phenol resveratrol[6,7], and the polyphenol diferuloylmethane (curcumin; CUR). The activation of STAT3 by CUR in DC is mediated through heme oxygenase 1 (HO1), a stress-response protein readily induced by CUR in vitro and in vivo
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