Luteolin inhibits NLRP3 inflammasome activation via blocking ASC oligomerization

Authors: NAM LEE, MI - Chonnam National University; LEE, YOUNGYOON - Chungbuk National University; WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; PAE, MUNKYONG - Chungbuk National University

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/2/2021
Publication Date: 3/8/2021
Citation: Nam Lee, M., Lee, Y., Wu, D., Pae, M. 2021. Luteolin inhibits NLRP3 inflammasome activation via blocking ASC oligomerization. Journal of Nutritional Biochemistry. 92:108614. https://doi.org/10.1016/j.jnutbio.2021.108614.
DOI: https://doi.org/10.1016/j.jnutbio.2021.108614

Interpretive Summary: The NLRP3 inflammasome is a complex of molecules which has been implicated in development of several chronic diseases. Luteolin, a naturally occurring compound widely found in many vegetables, is shown to have health benefit through its anti-inflammatory activity. Supported by the National Research Foundation of Korea (NRF) and the U.S. Department of Agriculture, researchers evaluated whether luteolin modulates NLRP3 inflammasome in a mouse model of postmenopausal obesity. The results showed that dietary supplementation with luteolin reduced NLRP3 inflammasome levels in adipose tissue. These findings support the regulatory role of luteolin in NLRP3 inflammasome activation and suggest its potential translational value in improving NLRP3-related diseases.

Technical Abstract: The NLRP3 inflammasome is a caspase-1 containing multi-protein complex that controls the release of IL-1beta and plays important roles in the innate immune response. Since NLRP3 inflammasome is implicated in the pathogenesis of a variety of diseases, it has become an increasingly interested target in developing therapies for multiple diseases. We reported the current study to determine how luteolin, a natural phenolic compound found in many vegetables and medicinal herbs, would modulate NLRP3 inflammasome in both the in vivo and in vitro settings. First, we found that a high-fat diet upregulated mRNA expression of NLRP3 inflammasome components Asc and Casp1 in adipose tissue of ovariectomized mice, which were greatly reduced by dietary supplementation with luteolin. Of note, Asc and Casp1 expression in adipose tissue correlated with mRNA levels of Adgre1 encoding F4/80, an established marker for mature macrophages. We also demonstrated that luteolin inhibited NLRP3 inflammasome-derived caspase-1 activation and IL-1beta secretion in J774A.1 macrophages upon diverse stimuli including ATP, nigericin, or silica crystals. Luteolin inhibited the activation step of NLRP3 inflammasome by interfering with ASC oligomerization. Taken together, these findings suggest that luteolin supplementation may suppress NLRP3 induction and activation process and thus potentially would be protective against NLRP3-mediated inflammatory diseases.