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Hydroxychloroquine Inhibits Macrophage Activation and Attenuates Renal Fibrosis After Ischemia-Reperfusion Injury
- Source :
- Frontiers in Immunology, Frontiers in Immunology, Vol 12 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media S.A., 2021.
-
Abstract
- Chronic kidney disease (CKD), which is associated with high morbidity, remains a worldwide health concern, while effective therapies remain limited. Hydroxychloroquine (HCQ), which mainly targets toll-like receptor-7 (TLR-7) and TLR-9, is associated with a lower risk of incident CKD. Taking into account that TLR-9 is involved in the development of renal fibrosis and serves as a potential therapy target for CKD, we investigated whether HCQ could attenuate CKD via TLR-9 signal pathway. The effects of HCQ on renal tubulointerstitial fibrosis were further explored using a mouse model of renal tubulointerstitial fibrosis after ischemia/reperfusion injury. Bone marrow-derived macrophages were isolated to explore the effects of HCQ in vitro. Judicious use of HCQ efficiently inhibited the activation of macrophages and MAPK signaling pathways, thereby attenuating renal fibrosis in vivo. In an in vitro model, results showed that HCQ promoted apoptosis of macrophages and inhibited activation of macrophages, especially M2 macrophages, in a dose-dependent manner. Because TLR-7 is not involved in the development of CKD post-injury, a TLR-9 knockout mouse was used to explore the mechanisms of HCQ. The effects of HCQ on renal fibrosis and macrophages decreased after depletion of TLR-9 in vivo and in vitro. Taken together, this study indicated that proper use of HCQ could be a new strategy for anti-fibrotic therapy and that TLR-9 could be a potential therapeutic target for CKD following acute kidney injury.
- Subjects :
- 0301 basic medicine
lcsh:Immunologic diseases. Allergy
hydroxychloroquine
MAP Kinase Signaling System
Immunology
Inflammation
macrophage
Pharmacology
Kidney
urologic and male genital diseases
03 medical and health sciences
Mice
0302 clinical medicine
Fibrosis
Renal fibrosis
Immunology and Allergy
Medicine
Animals
Original Research
Mice, Knockout
business.industry
Macrophages
fibrosis
Acute kidney injury
Hydroxychloroquine
Macrophage Activation
medicine.disease
Disease Models, Animal
030104 developmental biology
inflammation
030220 oncology & carcinogenesis
Reperfusion Injury
Tubulointerstitial fibrosis
Kidney Diseases
medicine.symptom
business
lcsh:RC581-607
Reperfusion injury
chronic kidney disease
Kidney disease
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....088149e392ad3de349e2344a5012d4c9