Inhibition of PD-1 Alters the SHP1/2-PI3K/Akt Axis to Decrease M1 Polarization of Alveolar Macrophages in Lung Ischemia–Reperfusion Injury
| العنوان: | Inhibition of PD-1 Alters the SHP1/2-PI3K/Akt Axis to Decrease M1 Polarization of Alveolar Macrophages in Lung Ischemia–Reperfusion Injury |
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| المؤلفون: | Xiaojing He, Jingyuan Xiao, Zhao Li, Mengling Ye, Jinyuan Lin, Zhen Liu, Yubing Liang, Huijun Dai, Ren Jing, Fei Lin |
| المصدر: | Inflammation. 46:639-654 |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Immunology, Immunology and Allergy |
| الوصف: | Abstract Polarization of alveolar macrophages (AMs) into the M1 phenotype contributes to inflammatory responses and tissue damage that occur during lung ischemia–reperfusion injury (LIRI). Programmed cell death factor-1 (PD-1) regulates polarization of macrophages, but its role in LIRI is unknown. We examined the role of PD-1 in AM polarization in models of LIRI in vivo and in vitro. Adult Sprague–Dawley rats were subjected to ischemia–reperfusion with or without pretreatment with a PD-1 inhibitor, SHP1/2 inhibitor, or Akt activator. Lung tissue damage and infiltration by M1-type AMs were assessed. As an in vitro complement to the animal studies, rat alveolar macrophages in culture were subjected to oxygen/glucose deprivation and reoxygenation. Levels of SHP1/2 and Akt proteins were evaluated using Western blots, while levels of pro-inflammatory cytokines were measured using enzyme-linked immunosorbent assays. Injury upregulated PD-1 both in vivo and in vitro. Inhibiting PD-1 reduced the number of M1-type AMs, expression of SHP1 and SHP2, and levels of inflammatory cytokines. At the same time, it partially restored Akt activation. Similar results were observed after inhibition of SHP1/2 or activation of the PI3K/Akt pathway. PD-1 promotes polarization of AMs to the M1 phenotype and inflammatory responses through the SHP1/2-PI3K/Akt axis. Inhibiting PD-1 may be an effective therapeutic strategy to limit LIRI. |
| تدمد: | 1573-2576 0360-3997 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe0ac0a0c1aaa21dddf7f39a56ccb2ff https://doi.org/10.1007/s10753-022-01762-6 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fe0ac0a0c1aaa21dddf7f39a56ccb2ff |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15732576 03603997 |
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