The role of IL-18 and IL-12 in the modulation of matrix metalloproteinases and their tissue inhibitors in monocytic cells.
The matrix metalloproteinases (MMP) are enzymes crucial for the physiological patrol as well as pathological chemotaxis of immune cells to target tissues. The present study examined differential effects of pro-inflammatory [IL-18, IL-12 and tumor necrosis factor (TNF)-alpha] versus anti-inflammatory (IL-4) cytokines on the modulation of MMP and their endogenous tissue inhibitors (TIMP) expression in the U937 cell line. IL-18 and IL-12 separately and synergistically enhanced MMP-2, while TNF-alpha led to the elevation of MMP-9. All pro-inflammatory cytokines enhanced MT1-MMP expression and IL-4 suppressed TNF-alpha-induced MMP-9 expression. This study demonstrated that elevated IL-18 and IL-12, and related pro-inflammatory activity, may be associated with aberrant MMP activity, suggesting modulation of MMP expression using IL-12 and IL-18 antagonists as future therapeutic strategies to attenuate inflammatory and autoimmune disorders.
Abraham
Michal
M
Neuroimmunology and Immunology Research Units, Carmel Medical Center, and Rappaport Institute for Research in the Medical Sciences, and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Shapiro
Sarah
S
Lahat
Nitza
N
Miller
Ariel
A
D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D020382:Interleukin-18 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D020382:Interleukin-18; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D015847:Interleukin-4; D020782:Matrix Metalloproteinases