Leptin promotes IL-18 secretion by activating the NLRP3 inflammasome in RAW 264.7 cells

Leptin is a cytokine-like hormone secreted by adipocytes, which serves to control energy expenditure and metabolism. In addition, leptin may modulate the innate and adaptive immune responses. The innate immune cell sensor nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is mainly expressed in myeloid immune cells, including macrophages. The NLRP3 inflammasome serves a pivotal role in the development and maintenance of autoimmunity and inflammation. The expression levels of caspase-1, apoptosis-associated speck-like protein containing a CARD, interleukin (IL)-18, IL-1 beta and leptin are significantly reduced in the white adipose tissue of nonsteroidal anti-inflammatory drug-activated gene-1 transgenic mice. However, the association between leptin and the NLRP3 inflammasome has not yet to be determined. The aim of the present study, was to explore the role of leptin on NLRP3 inflammasome. In order to do this, IL-1 beta and IL-18 expression levels were investigated in RAW 264.7 cells after incubation with leptin of increasing doses by Elisa or reverse transcription-quantitative polymerase chain reaction, and to assess whether IL-1 beta and IL-18 were affected after caspase-1 activity being inhibited by an inhibitor or by silencing NLRP3 expression. The results of the present study demonstrated that leptin enhanced the mRNA and protein expression levels of IL-18 in RAW 264.7 cells via activation of the NLRP3 inflammasome. This is achieved partly by enhancing the production of reactive oxygen species and K+ efflux. Therefore, leptin may be considered a novel activator and modulator of the NLRP3 inflammasome.