Interleukin-22 Attenuated Renal Tubular Injury in Aristolochic Acid Nephropathy via Suppressing Activation of NLRP3 Inflammasome
Aristolochic acid nephropathy (AAN), as a rapidly progressive interstitial nephropathy due to excessive ingestion of aristolochia herbal medications, has recently raised considerable concerns among clinicians and researchers as its underlying pathogenic mechanisms are largely unclear. In the current...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02277/full |
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| author | Shaofei Wang Shaofei Wang Jiajun Fan Jiajun Fan Xiaobin Mei Jingyun Luan Jingyun Luan Yubin Li Yubin Li Xuyao Zhang Xuyao Zhang Wei Chen Wei Chen Yichen Wang Yichen Wang Guangxun Meng Dianwen Ju Dianwen Ju |
| author_facet | Shaofei Wang Shaofei Wang Jiajun Fan Jiajun Fan Xiaobin Mei Jingyun Luan Jingyun Luan Yubin Li Yubin Li Xuyao Zhang Xuyao Zhang Wei Chen Wei Chen Yichen Wang Yichen Wang Guangxun Meng Dianwen Ju Dianwen Ju |
| author_sort | Shaofei Wang |
| collection | DOAJ |
| description | Aristolochic acid nephropathy (AAN), as a rapidly progressive interstitial nephropathy due to excessive ingestion of aristolochia herbal medications, has recently raised considerable concerns among clinicians and researchers as its underlying pathogenic mechanisms are largely unclear. In the current study, we identified NLRP3 inflammasome activation as a novel pathological mechanism of AAN. We found that NLRP3 inflammasome was aberrantly activated both in vivo and in vitro after AA exposure. Blockade of IL-1β and NLRP3 inflammasome activation by IL-1Ra significantly attenuated renal tubular injury and function loss in AA-induced nephropathy. Moreover, NLRP3 or Caspase-1 deficiency protected against renal injury in the mouse model of acute AAN, suggesting that the NLRP3 signaling pathway was probably involved in the pathogenesis of AAN. We also found that administration of IL-22 could markedly attenuate renal tubular injury in AAN. Notably, IL-22 intervention significantly alleviated renal fibrosis and dysfunction in AA-induced nephropathy. Furthermore, IL-22 largely inhibited renal activation of NLRP3 inflammasome in AA-induced nephropathy. These results indicated that IL-22 ameliorated renal tubular injury in AAN through suppression of NLRP3 inflammasome activation. In summary, this study identified renal activation of NLRP3 inflammasome as a novel mechanism underlying the pathogenesis of AAN, thus providing a potential therapeutic strategy for AAN based on suppression of NLRP3 inflammasome activation. |
| first_indexed | 2024-04-13T02:52:56Z |
| format | Article |
| id | doaj.art-21e3f69c5c614293be5458512ce52e36 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T02:52:56Z |
| publishDate | 2019-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-21e3f69c5c614293be5458512ce52e362022-12-22T03:05:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-09-011010.3389/fimmu.2019.02277471601Interleukin-22 Attenuated Renal Tubular Injury in Aristolochic Acid Nephropathy via Suppressing Activation of NLRP3 InflammasomeShaofei Wang0Shaofei Wang1Jiajun Fan2Jiajun Fan3Xiaobin Mei4Jingyun Luan5Jingyun Luan6Yubin Li7Yubin Li8Xuyao Zhang9Xuyao Zhang10Wei Chen11Wei Chen12Yichen Wang13Yichen Wang14Guangxun Meng15Dianwen Ju16Dianwen Ju17Minhang Hospital, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaMinhang Hospital, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaDepartment of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai, ChinaMinhang Hospital, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaMinhang Hospital, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaMinhang Hospital, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaMinhang Hospital, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaMinhang Hospital, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaUnit of Innate Immunity, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, ChinaMinhang Hospital, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaAristolochic acid nephropathy (AAN), as a rapidly progressive interstitial nephropathy due to excessive ingestion of aristolochia herbal medications, has recently raised considerable concerns among clinicians and researchers as its underlying pathogenic mechanisms are largely unclear. In the current study, we identified NLRP3 inflammasome activation as a novel pathological mechanism of AAN. We found that NLRP3 inflammasome was aberrantly activated both in vivo and in vitro after AA exposure. Blockade of IL-1β and NLRP3 inflammasome activation by IL-1Ra significantly attenuated renal tubular injury and function loss in AA-induced nephropathy. Moreover, NLRP3 or Caspase-1 deficiency protected against renal injury in the mouse model of acute AAN, suggesting that the NLRP3 signaling pathway was probably involved in the pathogenesis of AAN. We also found that administration of IL-22 could markedly attenuate renal tubular injury in AAN. Notably, IL-22 intervention significantly alleviated renal fibrosis and dysfunction in AA-induced nephropathy. Furthermore, IL-22 largely inhibited renal activation of NLRP3 inflammasome in AA-induced nephropathy. These results indicated that IL-22 ameliorated renal tubular injury in AAN through suppression of NLRP3 inflammasome activation. In summary, this study identified renal activation of NLRP3 inflammasome as a novel mechanism underlying the pathogenesis of AAN, thus providing a potential therapeutic strategy for AAN based on suppression of NLRP3 inflammasome activation.https://www.frontiersin.org/article/10.3389/fimmu.2019.02277/fullIL-22aristolochic acid nephropathyNLRP3 inflammasometubular injuryrenal function |
| spellingShingle | Shaofei Wang Shaofei Wang Jiajun Fan Jiajun Fan Xiaobin Mei Jingyun Luan Jingyun Luan Yubin Li Yubin Li Xuyao Zhang Xuyao Zhang Wei Chen Wei Chen Yichen Wang Yichen Wang Guangxun Meng Dianwen Ju Dianwen Ju Interleukin-22 Attenuated Renal Tubular Injury in Aristolochic Acid Nephropathy via Suppressing Activation of NLRP3 Inflammasome Frontiers in Immunology IL-22 aristolochic acid nephropathy NLRP3 inflammasome tubular injury renal function |
| title | Interleukin-22 Attenuated Renal Tubular Injury in Aristolochic Acid Nephropathy via Suppressing Activation of NLRP3 Inflammasome |
| title_full | Interleukin-22 Attenuated Renal Tubular Injury in Aristolochic Acid Nephropathy via Suppressing Activation of NLRP3 Inflammasome |
| title_fullStr | Interleukin-22 Attenuated Renal Tubular Injury in Aristolochic Acid Nephropathy via Suppressing Activation of NLRP3 Inflammasome |
| title_full_unstemmed | Interleukin-22 Attenuated Renal Tubular Injury in Aristolochic Acid Nephropathy via Suppressing Activation of NLRP3 Inflammasome |
| title_short | Interleukin-22 Attenuated Renal Tubular Injury in Aristolochic Acid Nephropathy via Suppressing Activation of NLRP3 Inflammasome |
| title_sort | interleukin 22 attenuated renal tubular injury in aristolochic acid nephropathy via suppressing activation of nlrp3 inflammasome |
| topic | IL-22 aristolochic acid nephropathy NLRP3 inflammasome tubular injury renal function |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02277/full |
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