15-Lipoxygenase-1 induces expression and release of chemokines in cultured human lung epithelial cells.
15-Lipoxygenase-1 (15-LOX-1) has been proposed to be involved in various physiological and pathophysiological activities such as inflammation, atherosclerosis, cell maturation, and tumorigenesis. Asthma and chronic obstructive pulmonary disease are associated with increased expression of 15-LOX-1 in bronchial epithelial cells, but the potential functions of 15-LOX-1 in airway epithelial cells have not been well clarified. To study the function of 15-LOX-1 in bronchial epithelial cells, we ectopically expressed 15-LOX-1 in the human lung epithelial cell line A549. We found that overexpression of 15-LOX-1 in A549 cells leads to increased release of the chemokines MIP-1alpha, RANTES, and IP-10, and thereby to increased recruitment of immature dendritic cells, mast cells, and activated T cells. These results suggest that an increased expression and activity of 15-LOX-1 in lung epithelial cells is a proinflammatory event in the pathogenesis of asthma and other inflammatory lung disorders.
Department of Medicine, Division of Hematology, Hematology Laboratory, Center for Molecular Medicine, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden. Cheng.liu@ki.se
Cheng
C
Liu
Dawei
D
Xu
Li
L
Liu
Frida
F
Schain
Asa
A
Brunnström
Magnus
M
Björkholm
Hans-Erik
HE
Claesson
Jan
J
Sjöberg
D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008168:Lung / Q000166:cytology*; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D018925:Chemokines; D016328:NF-kappa B; D001093:Arachidonate 15-Lipoxygenase