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Published on: March 30, 2018
Mesencephalic astrocyte-derived neurotrophic factor attenuates acute lung injury via inhibiting macrophages'
Qi-Ying Shen1, Dong Wang2, Han-Yang Xu3
1Department of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Department of Anesthesiology, the Fourth Affiliated Hospital of Anhui Medical University, Hefei 230000, China; Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei 230022, China.
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.
Insights
Mesencephalic astrocyte-derived neurotrophic factor (MANF) suppresses acute lung injury (ALI) by reducing inflammation and inhibiting macrophage polarization. MANF may be a potential therapeutic target for ALI treatment.
Area of Science:
- Pulmonary Medicine
- Immunology
- Molecular Biology
Background:
- Acute lung injury (ALI) is a critical respiratory condition lacking effective treatments.
- Mesencephalic astrocyte-derived neurotrophic factor (MANF) has shown anti-inflammatory properties in other conditions.
- The role of MANF in ALI has not been previously investigated.
Purpose of the Study:
- To investigate the role and therapeutic potential of MANF in acute lung injury.
- To determine MANF's effect on macrophage polarization and NF-κB signaling in ALI.
Main Methods:
- Collected bronchoalveolar lavage fluid (BALF) from patients with and without pulmonary inflammation.
- Induced ALI in mice using lipopolysaccharide (LPS).
- Utilized mono-macrophage-specific MANF knockout (MKO) mice and administered recombinant human MANF protein.
Main Results:
- Endogenous MANF levels were elevated in human BALF and mouse lung tissues during inflammation, particularly in macrophages.
- MANF deficiency in macrophages exacerbated lung inflammation and ALI.
- MANF administration reduced LPS-induced lung injury, inhibited M1 macrophage polarization, and suppressed NF-κB pathway activation.
Conclusions:
- MANF acts as a suppressor in ALI by inhibiting NF-κB activation and macrophage polarization.
- MANF demonstrates potential as a novel therapeutic target for acute lung injury.
- Further research into MANF's mechanisms could illuminate new therapeutic strategies for ALI.
