Journal of Inflammation Research (Oct 2022)
Inhibition of Dectin-1 Alleviates Neuroinflammatory Injury by Attenuating NLRP3 Inflammasome-Mediated Pyroptosis After Intracerebral Hemorrhage in Mice: Preliminary Study Results
Abstract
Zhiquan Ding1 *, Zhenzhong Zhong1 *, Jun Wang1 *, Run Zhang,2 Jinlian Shao,3 Yulong Li,1 Guiwei Wu,1 Huiru Tu,1 Wen Yuan,4 Haitao Sun,1,5 Qinghua Wang1,3 1Neurosurgery Center, Department of Neurotrauma and Neurocritical Care Medicine, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Neurosurgery Center, Department of Neuro-oncological Surgery, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Emergency, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Laboratory Animal Center, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinghua Wang; Haitao Sun, Neurosurgery Center, Department of Neurotrauma and Neurocritical Care Medicine, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China, Email [email protected]; [email protected]: Neuroinflammation plays an important role following intracerebral hemorrhage (ICH). NLRP3 inflammasome-mediated pyroptosis contributes to the mechanism of neuroinflammation. It has been reported that dendritic cell-associated C-type lectin-1 (Dectin-1) activation triggers inflammation in neurological diseases. However, the role of Dectin-1 on NLRP3 inflammasome-mediated pyroptosis after ICH remains unclear. Here, we aimed to explore the effect of Dectin-1 on NLRP3 inflammasome-mediated pyroptosis and neuroinflammation after ICH.Methods: Adult male C57BL/6 mice were used to establish the ICH model. Laminarin, an inhibitor of Dectin-1, was administered for intervention. Expression of Dectin-1 was evaluated by Western blot and immunofluorescence. Brain water content and neurobehavioral function were tested to assess brain edema and neurological performance. Western blot was conducted to evaluate the level of GSDMD-N. ELISA kits were used to measure the levels of IL-1β and IL-18. qRT–PCR and Western blot were performed to evaluate the expressions of NLRP3 inflammasome, IL-1β, and IL-18.Results: The expression of Dectin-1 increased following ICH, and Dectin-1 was expressed on microglia. In addition, inhibition of Dectin-1 by laminarin decreased brain edema and neurological impairment after ICH. Moreover, inhibition of Dectin-1 decreased the expression of pyroptosis-related protein, GSDMD-N, and inflammatory cytokines (IL-1β and IL-18). Mechanistically, Dectin-1 blockade inhibits NLRP3 inflammasome activation, thereby alleviating neuroinflammatory injury by attenuating NLRP3 inflammasome-mediated pyroptosis both in vivo and in vitro.Conclusion: Our study indicates that the inhibition of Dectin-1 alleviates neuroinflammation by attenuating NLRP3 inflammasome-mediated pyroptosis after ICH.Keywords: intracerebral hemorrhage, Dectin-1, NLRP3 inflammasome, pyroptosis, microglia
