IL-18 increases invasiveness of HL-60 myeloid leukemia cells: up-regulation of matrix metalloproteinases-9 (MMP-9) expression.
Similar to matrix metalloproteinases (MMP-9/-2), IL-18 was overexpressed in some hematologic malignancies such as acute myeloid leukemia (AML), which is associated with a poor clinical outcome. To establish a possible functional relationship between IL-18 and MMPs in myeloid leukemia, we used semi-quantitative PCR and zymographic analysis to examine whether IL-18 stimulates human myeloid leukemia cell line HL-60 to produce MMPs and/or specific tissue inhibitors (TIMPs), and to degrade extracellular matrix (ECM) gel in vitro. In the ECM invasion assay IL-18 significantly up-regulated transmigration of HL-60 cells, which in turn was inhibited by a synthetic MMP inhibitor: O-phenanthroline (o-PE), anti-MMP-9, anti-MMP-2 as well as anti-IL-18 monoclonal antibody (McAb), respectively, suggesting that induction of gelatinases by IL-18 leads to ECM degradation by these cells. Moreover, IL-18 could significantly increase MMP-9 but not MMP-2 production at both mRNA and/or protein level, slightly up-regulate TIMP-1 mRNA, and clearly induce TIMP-2 mRNA secretion. We postulate that IL-18 may in part play a role in the clinical aggressiveness of human myeloid leukemia by stimulating MMP-9 production.
Zhang
Bin
B
National Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, PR China.
Wu
Ke-Fu
KF
Cao
Zhen-Yu
ZY
Rao
Qing
Q
Ma
Xiao-Tong
XT
Zheng
Guo-Guang
GG
Li
Ge
G
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D005109:Extracellular Matrix / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology / Q000502:physiology*; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020382:Interleukin-18 / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000201:enzymology* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D010618:Phenanthrolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D020382:Interleukin-18; D061965:Matrix Metalloproteinase Inhibitors; D010618:Phenanthrolines; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C025205:1,10-phenanthroline