Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 27, Issue 1, Pages 148-153Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2015.05.008
Keywords
Fluorofenidone; IL-1 beta; Inflammasome
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Funding
- National Natural Science Foundation of China [81273575, 81200048]
- Doctoral Foundation of the Ministry of Education of China [20120162130001]
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Interleukin-1 beta (IL-1 beta) is a potent pro-inflammatory and pro-fibrotic cytokine that plays an important role in renal fibrosis. Fluorofenidone (AKF-PD) is a novel pyridone agent that exerts a strong renal anti-fibrotic effect. We previously found that administration of AKF-PD could significantly attenuate IL-1 beta production in vitro and in vivo. However, the underlying mechanism is not fully understood. Here we show that AKF-PD has no effect on the expression of pro-IL-1 beta in activated mouse macrophages in vitro. Instead, AKF-PD inhibits the inflammasome, lowering caspase-1 levels and thereby decreasing cleavage of pro-IL-1 beta into IL-1 beta. AKF-PD was found to block inflammasome activity induced by various signals, including ATP, alum crystals, and Salmonella typhimurium. These results provide a novel mechanistic insight into how AKF-PD exerts its anti-inflammatory and anti-fibrotic activities, and suggest that AKF-PD might block IL-1 beta production via suppression of inflammasomes in renal fibrosis. In addition, the results suggest that AKF-PD may be of therapeutic potential in other inflammasome-related diseases. (C) 2015 Elsevier B.V. All rights reserved.
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