IL-20, an anti-angiogenic cytokine that inhibits COX-2 expression.
COX-2 overexpression and subsequent PGE(2) production are frequently associated with non-small cell lung cancer and are implicated in tumor-mediated angiogenesis. Here, we report for the first time that IL-20 downregulates COX-2 and PGE(2) in human bronchial epithelial and endothelial cells. Flow cytometry analysis suggests that IL-20-dependent inhibition of COX-2/PGE(2) occurs through the IL-22R1/IL-20R2 dimers. In addition, we report that IL-20 exerts anti-angiogenic effects, inhibiting experimental angiogenesis. IL-20-mediated inhibition of PMA-induced angiogenesis occurs through the COX-2 regulatory pathway. Altogether our findings revealed that IL-20 is a negative modulator of COX-2/PGE(2) and inhibits angiogenesis.
Heuzé-Vourc'h
Nathalie
N
Division of Pulmonary and Critical Care Medicine, Department of Medicine, UCLA, Los Angeles, CA, USA.
Liu
Ming
M
Dalwadi
Harnisha
H
Baratelli
Felicita E
FE
Zhu
Li
L
Goodglick
Lee
L
Põld
Mehis
M
Sharma
Sherven
S
Ramirez
Ruben D
RD
Shay
Jerry W
JW
Minna
John D
JD
Strieter
Robert M
RM
Dubinett
Steven M
SM
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000008:administration & dosage; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007378:Interleukins / Q000008:administration & dosage*; D008565:Membrane Proteins; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D016207:Cytokines; D007378:Interleukins; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C422042:interleukin 20