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Published on: February 25, 2014
Progranulin Ameliorates Lung Inflammation in an LPS-induced Acute Lung Injury Mouse Model by Modulating Macrophage
Jingjing Lu1, Jianhao Huang1, Mengtian Shan1
1Department of Respiratoryand Critical Care Medicine, Shanghai East Hospital, School of Medicine, To ngji University, Pudong, Shanghai, and Department of Respiratory Medicine, The First Affiliated Hospital USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Objective:
Progranulin (PGRN) has been confirmed to exhibit anti-inflammatory activity. Nevertheless, the mechanisms of PGRN in acute lung injury (ALI) remain uncertain. The aim of this study was to explore the role of PGRN in a lipopolysaccharide (LPS)-induced ALI model and in primary bone marrow-derived macrophages, as well as to investigate the underlying mechanism of PGRN.
Methods:
Mice were treated with recombinant PGRN protein to detect the effect of PGRN on mouse ALI. Bronchial alveolar lavage fluid (BALF) was analyzed to quantify the inflammatory cytokines, and the lung wet-to-dry ratio was calculated to assess the degree of pulmonary edema. Histological staining was completed on the lung tissues. CCK-8 assay was used to measure cell viability. Western blotting and quantitative polymerase chain reaction were performed to study the transcriptomic profiles during the MAPK pathway.
Results:
Recombinant human PGRN significantly suppressed cellular inflammatory response, increased lung permeability, and reduced the expression of inflammatory proteins in the BALF and serum, which further improved survival time. Also, PGRN inhibited the LPS-induced M1 marker gene expression and enhanced the M2 marker gene expression in vivo and in vitro. Further analysis revealed that PGRN suppresses the activity of the MAPK pathway in LPS-treated macrophages in a dose-dependent manner.
Conclusion:
PGRN exhibited anti-inflammatory activity and regulated macrophage polarization by suppressing the phosphorylation of the MAPK pathway.

