NLRP3 ablation enhances tolerance in heat stroke pathology by inhibiting IL-1β-mediated neuroinflammation

Zhang，Zi Teng1; Gu，Xiao Lei2; Zhao，Xin1; He，Xian3,4; Shi，Hao Wei5; Zhang，Kun1; Zhang，Yi Ming1; Su，Yi Nan1; Zhu，Jiang Bo6; Li，Zhi Wei1; Li，Guo Bao7

2021-12-01

10.1186/s12974-021-02179-y

Journal of Neuroinflammation   影响因子和分区

1742-2094

Background: Patients with prior illness are more vulnerable to heat stroke-induced injury, but the underlying mechanism is unknown. Recent studies suggested that NLRP3 inflammasome played an important role in the pathophysiology of heat stroke. Methods: In this study, we used a classic animal heat stroke model. Prior infection was mimicked by using lipopolysaccharide (LPS) or lipoteichoic acid (LTA) injection before heat stroke (LPS/LTA 1 mg/kg). Mice survival analysis curve and core temperature (T) elevation curve were produced. NLRP3 inflammasome activation was measured by using real-time PCR and Western blot. Mice hypothalamus was dissected and neuroinflammation level was measured. To further demonstrate the role of NLRP3 inflammasome, Nlrp3 knockout mice were used. In addition, IL-1β neutralizing antibody was injected to test potential therapeutic effect on heat stroke. Results: Prior infection simulated by LPS/LTA injection resulted in latent inflammation status presented by high levels of cytokines in peripheral serum. However, LPS/LTA failed to cause any change in animal survival rate or body temperature. In the absence of LPS/LTA, heat treatment induced heat stroke and animal death without significant systemic or neuroinflammation. Despite a decreased level of IL-1β in hypothalamus, Nlrp3 knockout mice demonstrated no survival advantage under mere heat exposure. In animals with prior infection, their heat tolerance was severely impaired and NLRP3 inflammasome induced neuroinflammation was detected. The use of Nlrp3 knockout mice enhanced heat tolerance and alleviated heat stroke-induced death by reducing mice hypothalamus IL-1β production with prior infection condition. Furthermore, IL-1β neutralizing antibody injection significantly extended endotoxemic mice survival under heat stroke. Conclusions: Based on the above results, NLRP3/IL-1β induced neuroinflammation might be an important mechanistic factor in heat stroke pathology, especially with prior infection. IL-1β may serve as a biomarker for heat stroke severity and potential therapeutic method.

Heatstroke IL-1β Neuroinflammation NLRP3 inflammasome

SCI

英语

第一

WOS:000660897300002

2-s2.0-85107324215

Scopus

1.Department of Hepato-Biliary Surgery,Shenzhen Third People’s Hospital,The Second Affiliated Hospital,Southern University of Science and Technology,Shenzhen,No.29 Bulan Road, Longgang District,518055,China
2.Department of Pharmacy,The Affiliated Tumor Hospital of Zhengzhou University,Zhengzhou,450008,China
3.School of Pharmacy,Dali University,Dali,671000,China
4.Fifth Medical Center of PLA General Hospital,Beijing,100000,China
5.Department of Neurosurgery,Hebei Provincial People’s Hospital,Shijiazhuang,050051,China
6.Department of Health Toxicology,Faculty of Navy Medicine,Navy Medical University,Shanghai,200433,China
7.Department of Lung Disease,Shenzhen Third People’s Hospital,The Second Affiliated Hospital,Southern University of Science and Technology,Shenzhen,No.29 Bulan Road, Longgang District,518055,China

Zhang，Zi Teng,Gu，Xiao Lei,Zhao，Xin,et al. NLRP3 ablation enhances tolerance in heat stroke pathology by inhibiting IL-1β-mediated neuroinflammation[J]. Journal of Neuroinflammation,2021,18(1).

Zhang，Zi Teng.,Gu，Xiao Lei.,Zhao，Xin.,He，Xian.,Shi，Hao Wei.,...&Li，Guo Bao.(2021).NLRP3 ablation enhances tolerance in heat stroke pathology by inhibiting IL-1β-mediated neuroinflammation.Journal of Neuroinflammation,18(1).

Zhang，Zi Teng,et al."NLRP3 ablation enhances tolerance in heat stroke pathology by inhibiting IL-1β-mediated neuroinflammation".Journal of Neuroinflammation 18.1(2021).