| Autor: |
Shuzhao Zhuang, Aaron Russell, Yifan Guo, Yingying Xu, Weihua Xiao |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cellular & Molecular Biology Letters, Vol 28, Iss 1, Pp 1-19 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1689-1392 |
| DOI: |
10.1186/s11658-023-00439-8 |
| Popis: |
Abstract Background Innate immune responses play essential roles in skeletal muscle recovery after injury. Programmed cell death protein 1 (PD-1) contributes to skeletal muscle regeneration by promoting macrophage proinflammatory to anti-inflammatory phenotype transition. Interferon (IFN)-γ induces proinflammatory macrophages that appear to hinder myogenesis in vitro. Therefore, we tested the hypothesis that blocking IFN-γ in PD-1 knockout mice may dampen inflammation and promote skeletal muscle regeneration via regulating the macrophage phenotype and neutrophils. Methods Anti-IFN-γ antibody was administered in PD-1 knockout mice, and cardiotoxin (CTX) injection was performed to induce acute skeletal muscle injury. Hematoxylin and eosin (HE) staining was used to view morphological changes of injured and regenerated skeletal muscle. Masson’s trichrome staining was used to assess the degree of fibrosis. Gene expressions of proinflammatory and anti-inflammatory factors, fibrosis-related factors, and myogenic regulator factors were determined by real-time polymerase chain reaction (PCR). Changes in macrophage phenotype were examined by western blot and real-time PCR. Immunofluorescence was used to detect the accumulation of proinflammatory macrophages, anti-inflammatory macrophages, and neutrophils. Results IFN-γ blockade in PD-1 knockout mice did not alleviate skeletal muscle damage or improve regeneration following acute cardiotoxin-induced injury. Instead, it exacerbated skeletal muscle inflammation and fibrosis, and impaired regeneration via inhibiting macrophage accumulation, blocking macrophage proinflammatory to anti-inflammatory transition, and enhancing infiltration of neutrophils. Conclusion IFN-γ is crucial for efficient skeletal muscle regeneration in the absence of PD-1. |
| Databáze: |
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| Externí odkaz: |
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