Mesencephalic astrocyte-derived neurotrophic factor attenuates acute lung injury via inhibiting macrophages’ activation - 27/05/22
Abstract |
Acute lung injury (ALI) is an urgent respiratory disease without effective treatment. Mesencephalic astrocyte-derived neurotrophic factor (MANF)has been demonstrated to play a suppressive role in some inflammatory conditions. However, the effect of MANF on ALI has not yet been reported. In this study, we collected bronchoalveolar lavage fluid (BALF) from the patients with or without pulmonary inflammation, and used lipopolysaccharide (LPS) to induce mice ALI model. Mono-macrophage-specific MANF knockout (MKO) mice were constructed and recombinant human MANF protein was used to ALI mice. We found that the endogenous MANF protein in both human BALF and mice lung tissues was increased in inflammatory conditions. MANF level in the macrophages of inflammatory lung was higher than that in normal controls in both human and mice. MANF deficiency in macrophages induced lung inflammation and aggravated LPS-induced lung injury. MANF lowered LPS-induced lung injury, inhibited macrophage polarization to M1 functional type. Meanwhile, MANF inhibited-LPS induced activation of NF-κB signal pathway by down regulating phosphorylated p65in lung tissue and macrophages. These results indicate that MANF acts as a suppressor in ALI via negatively regulating NF-κB activation and macrophages polarization, which may be a novel potential target and shed light on ALI therapy.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | MANF was up-regulated in inflammatory lung injury. |
• | MANF deficiency in macrophages induced lung inflammation and aggravated LPS-induced lung injury in mice. |
• | Recombinant human MANF attenuated LPS-induced lung injury in mice. |
• | MANF deficiency in macrophages promoted macrophages to M1differentiation in lung tissues of ALI mice. |
• | Recombinant human MANF restricted macrophages to M1 differentiation in lung tissues of ALI mice. |
Keywords : Mesencephalic astrocyte-derived neurotrophic factor, Acute lung injury, Macrophage, NF-κB signal pathway
Plan
☆ | Clinical trial number: ChiCTR1800017141 (registered at Chinese Clinical Trial Registry). |
Vol 150
Article 112943- juin 2022 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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