Histidine ameliorates elastase- and lipopolysaccharide-induced lung inflammation by inhibiting the activation of the NLRP3 inflammasome.

ABSTRACT

Histidine treatment has anti-inflammatory effects on several diseases such as colitis and obesity. We revealed that histidine levels were decreased in the serum of patients with chronic obstructive pulmonary disease (COPD) in our previous study. However, whether histidine confers protection against COPD is unclear. In the present study, we evaluated the protective effects of histidine in a porcine pancreatic elastase- and lipopolysaccharide-induced COPD mouse model. We found that the serum histidine concentration was decreased in COPD mice. Histidine supplementation improved the COPD mouse lung function and reduced the inflammatory cell counts and production of cytokines in bronchoalveolar lavage fluid. In addition, histidine treatment ameliorated lung inflammation by inhibiting the nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 inflammasome activation both in vivo and in vitro. Furthermore, we found that the potential anti-inflammatory mechanism involved the upregulation of silent information regulator factor 2-related enzyme 1. These results suggest that histidine may be a valuable therapeutic target for COPD.