IL20Rb aggravates pulmonary fibrosis through enhancing bone marrow derived profibrotic macrophage activation.
Pharmacol Res
; 203: 107178, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38583686
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is one of the most fatal chronic interstitial lung diseases with unknown pathogenesis, current treatments cannot truly reverse the progression of the disease. Pulmonary macrophages, especially bone marrow derived pro-fibrotic macrophages, secrete multiple kinds of profibrotic mediators (SPP1, CD206, CD163, IL-10, CCL18
), thus further promote myofibroblast activation and fibrosis procession. IL20Rb is a cell-surface receptor that belongs to IL-20 family. The role of IL20Rb in macrophage activation and pulmonary fibrosis remains unclear. In this study, we established a bleomycin-induced pulmonary fibrosis model, used IL4/13-inducing THP1 cells to induce profibrotic macrophage (M2-like phenotype) polarization models. We found that IL20Rb is upregulated in the progression of pulmonary fibrosis, and its absence can alleviate the progression of pulmonary fibrosis. In addition, we demonstrated that IL20Rb promote the activation of bone marrow derived profibrotic macrophages by regulating the Jak2/Stat3 and Pi3k/Akt signaling pathways. In terms of therapeutic strategy, we used IL20Rb neutralizing antibodies for animal administration, which was found to alleviate the progression of IPF. Our results suggest that IL20Rb plays a profibrotic role by promoting profibrotic macrophage polarization, and IL20Rb may become a potential therapeutic target for IPF. Neutralizing antibodies against IL20Rb may become a potential drug for the clinical treatment of IPF.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Bleomicina
/
Activación de Macrófagos
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Macrófagos
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Pharmacol Res
Asunto de la revista:
FARMACOLOGIA
Año:
2024
Tipo del documento:
Article