1. Academic Validation
  2. Contribution of IL-33/ILC2-mediated Th2 cytokines during the progression of minimal change disease

Contribution of IL-33/ILC2-mediated Th2 cytokines during the progression of minimal change disease

  • Int Immunopharmacol. 2022 Dec 15;114:109493. doi: 10.1016/j.intimp.2022.109493.
Cui Liu 1 Li Liu 2 Yanping Huang 2 Ruiming Shi 2 Yue Wu 3 Intan Hakimah Binti Ismail 4
Affiliations

Affiliations

  • 1 Department of Pediatrics, Xi'an International Medical Center Hospital, Xi'an, Shaanxi 710100, China.
  • 2 Department of Pediatrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
  • 3 Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
  • 4 Department of Pediatrics, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. Electronic address: intanhakimah@163.com.
Abstract

Minimal change disease (MCD) is a common type of nephrotic syndrome with high recurrence rate. This study aims to explore the impacts of interleukin (IL)-33 in MCD and to discuss its potential mechanism. In adriamycin (ADM) and puromycin aminonucleoside (PAN)-induced MCD rat model, IL-33 was used for treatment. H&E staining was applied for detecting histological changes. Critical proteins were examined by western blot. Corresponding commercial kits tested oxidative stress- and inflammation-related factors. Cell Apoptosis was measured by TUNEL assay. ADM-induced podocyte injury model was establish to mimic MCD in vitro. Cell proliferation and Apoptosis were detected by CCK-8 and TUNEL assays. Finally, podocyte was stimulated by innate lymphoid type-2 cells-secreted Th2 cytokines (ILC2s: IL-13 and IL-5 respectively), with or without incubation with M1 macrophage medium to further explore the immune-regulation of ILC2s behind the inflammatory environment of MCD. It was found that PAN-induced kidney jury, inflammation, oxidative stress and Apoptosis were severer than ADM, and IL-33 treatment significantly alleviated the above injuries in PAN and ADM-induced MCD rat model. Moreover, IL-33 reversed the reduced viability and increased oxidative stress and Apoptosis in ADM-induced podocyte injury model. Further, the capacities of IL-13 alone in inducing M1/M2 macrophage polarization, Apoptosis, inflammation, kidney injury and reducing cell viability are stronger than IL-5. However, IL-13 reversed reduced cell viability and stimulated Apoptosis, inflammation, kidney injury mediated by co-incubation with M1-conditioned medium. Collectively, IL-33 might protect against immunologic injury in MCD via mediating ILC2s-secreted IL-13.

Keywords

IL-13; IL-33; ILC2s; Inflammation; Minimal change disease.

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