Vieira Angélica T, Galvão Izabela, Macia Laurence M, Sernaglia Érica M, Vinolo Marco Aurélio R, Garcia Cristiana C, Tavares Luciana P, Amaral Flávio A, Sousa Lirlândia P, Martins Flaviano S, Mackay Charles R, Teixeira Mauro M
Immunopharmacology Group, Department of Biochemistry and Immunology, Federal University of Minas Gerais, Minas Gerais, Brazil.
Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Minas Gerais, Brazil.
J Leukoc Biol. 2017 Jan;101(1):275-284. doi: 10.1189/jlb.3A1015-453RRR. Epub 2016 Aug 5.
Gout is a disease characterized by the deposition of monosodium urate (MSU) crystals in the joints. Continuous gout episodes may lead to unresolved inflammatory responses and tissue damage. We investigated the effects of a high-fiber diet and acetate, a short-chain fatty acid (SCFA) resulting from the metabolism of fiber by gut microbiota, on the inflammatory response in an experimental model of gout in mice. Injection of MSU crystals into the knee joint of mice induced neutrophil influx and inflammatory hypernociception. The onset of inflammatory response induced by MSU crystals was not altered in animals given a high-fiber diet, but the high-fiber diet induced faster resolution of the inflammatory response. Similar results were obtained in animals given the SCFA acetate. Acetate was effective, even when given after injection of MSU crystals at the peak of the inflammatory response and induced caspase-dependent apoptosis of neutrophils that accounted for the resolution of inflammation. Resolution of neutrophilic inflammation was associated with decreased NF-κB activity and enhanced production of anti-inflammatory mediators, including IL-10, TGF-β, and annexin A1. Acetate treatment or intake of a high-fiber diet enhanced efferocytosis, an effect also observed in vitro with neutrophils treated with acetate. In conclusion, a high-fiber diet or one of its metabolic products, acetate, controls the inflammatory response to MSU crystals by favoring the resolution of the inflammatory response. Our studies suggest that what we eat plays a determinant role in our capacity to fine tune the inflammatory response.
痛风是一种以单钠尿酸盐（MSU）晶体在关节中沉积为特征的疾病。持续的痛风发作可能导致炎症反应无法消退和组织损伤。我们在小鼠痛风实验模型中研究了高纤维饮食以及由肠道微生物群对纤维代谢产生的短链脂肪酸（SCFA）——乙酸盐对炎症反应的影响。向小鼠膝关节注射MSU晶体会诱导中性粒细胞流入和炎症性痛觉过敏。给予高纤维饮食的动物中，由MSU晶体诱导的炎症反应的起始并未改变，但高纤维饮食促使炎症反应更快消退。给予SCFA乙酸盐的动物也得到了类似结果。即使在炎症反应高峰期注射MSU晶体后给予乙酸盐也有效果，并且它会诱导中性粒细胞发生半胱天冬酶依赖性凋亡，这促成了炎症的消退。中性粒细胞性炎症的消退与核因子-κB（NF-κB）活性降低以及包括白细胞介素-10（IL-10）、转化生长因子-β（TGF-β）和膜联蛋白A1在内的抗炎介质产生增加有关。乙酸盐处理或高纤维饮食摄入增强了噬菌作用，在用乙酸盐处理的中性粒细胞的体外实验中也观察到了这种效果。总之，高纤维饮食或其代谢产物之一乙酸盐通过促进炎症反应的消退来控制对MSU晶体的炎症反应。我们的研究表明，我们的饮食在微调炎症反应的能力方面起着决定性作用。
