The FGL2/fibroleukin prothrombinase is involved in alveolar macrophage activation in COPD through the MAPK pathway.
Fibrinogen-like protein 2 (FGL2)/fibroleukin has been reported to play a vital role in the pathogenesis of some critical inflammatory diseases by possessing immunomodulatory activity through the mediation of "immune coagulation" and the regulation of maturation and proliferation of immune cells. We observed upregulated FGL2 expression in alveolar macrophages from peripheral lungs of chronic obstructive pulmonary disease (COPD) patients and found a correlation between FGL2 expression and increased macrophage activation markers (CD11b and CD14). The role of FGL2 in the activation of macrophages was confirmed by the detection of significantly decreased macrophage activation marker (CD11b, CD11c, and CD71) expression as well as the inhibition of cell migration and inflammatory cytokine (IL-8 and MMP-9) production in an LPS-induced FGL2 knockdown human monocytic leukemia cell line (THP-1). Increased FGL2 expression co-localized with upregulated phosphorylated p38 mitogen-activated protein kinase (p38-MAPK) in the lung tissues from COPD patients. Moreover, FGL2 knockdown in THP-1 cells significantly downregulated LPS-induced phosphorylation of p38-MAPK while upregulating phosphorylation of c-Jun N-terminal kinase (JNK). Thus, we demonstrate that FGL2 plays an important role in macrophage activation in the lungs of COPD patients through MAPK pathway modulation.
Liu
Yanling
Y
Department and Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
Xu
Sanpeng
S
Xiao
Fei
F
Xiong
Yan
Y
Wang
Xiaojin
X
Gao
Sui
S
Yan
Weiming
W
Ning
Qin
Q
D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005260:Female; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000201:enzymology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000276:immunology*; D013925:Thromboplastin / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C095202:FGL2 protein, human; D008070:Lipopolysaccharides; D005340:Fibrinogen; D013925:Thromboplastin; D048051:p38 Mitogen-Activated Protein Kinases