The Journal of Immunology, Vol 144, Issue 9 3518-3522, Copyright © 1990 by American Association of Immunologists

ARTICLES

Inhibition of phospholipase activity in human monocytes by IFN-gamma blocks endogenous prostaglandin E2-dependent collagenase production

LM Wahl, ME Corcoran, SE Mergenhagen and DS Finbloom
Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.

Previous studies from our laboratory have demonstrated that exposure of human monocytes to a stimulant, such as Con A, results in the production of the enzyme collagenase through PGE2-dependent pathway. Inasmuch as rIFN-gamma has been shown to modulate monocyte/macrophage PG synthesis, we examined the effect of rIFN-gamma on the activation sequence leading to collagenase production. The addition of rIFN-gamma (10 to 1000 U/ml) to Con A-stimulated monocytes resulted in a dose- dependent inhibition of PGE2 and collagenase synthesis. The suppression of collagenase production by rIFN-gamma was related to its ability to reduce PGE2 levels as demonstrated by the restoration of collagenase activity by the addition of PGE2. HPLC analysis of the arachidonic acid (AA) metabolites released by monocytes showed that rIFN-gamma caused a reduction in the release of AA and products of the cyclooxygenase and lipoxygenase pathways. These data indicated that rIFN-gamma decreased eicosanoid production by inhibiting the release of AA from phospholipids. This conclusion was supported by the reduction in membrane bound phospholipase activity in rIFN-gamma-treated monocytes. Moreover, the inhibition by rIFN-gamma of PGE2 and collagenase was reversed by the addition of phospholipase A2. Our findings demonstrate that rIFN-gamma inhibits phospholipase activity in activated monocytes and as a result blocks PGE2-dependent collagenase synthesis.

This article has been cited by other articles:

				P. T. G. Elkington, J. E. Emerson, L. D. C. Lopez-Pascua, C. M. O'Kane, D. E. Horncastle, J. J. Boyle, and J. S. Friedland Mycobacterium tuberculosis Up-Regulates Matrix Metalloproteinase-1 Secretion from Human Airway Epithelial Cells via a p38 MAPK Switch J. Immunol., October 15, 2005; 175(8): 5333 - 5340. [Abstract] [Full Text] [PDF]

				M. Zhou, Y. Zhang, J. A. Ardans, and L. M. Wahl Interferon-{gamma} Differentially Regulates Monocyte Matrix Metalloproteinase-1 and -9 through Tumor Necrosis Factor-{alpha} and Caspase 8 J. Biol. Chem., November 14, 2003; 278(46): 45406 - 45413. [Abstract] [Full Text] [PDF]

				G. G. Vaday, S. Franitza, H. Schor, I. Hecht, A. Brill, L. Cahalon, R. Hershkoviz, and O. Lider Combinatorial signals by inflammatory cytokines and chemokines mediate leukocyte interactions with extracellular matrix J. Leukoc. Biol., June 1, 2001; 69(6): 885 - 892. [Abstract] [Full Text] [PDF]

				G. G. Vaday, H. Schor, M. A. Rahat, N. Lahat, and O. Lider Transforming growth factor-{beta} suppresses tumor necrosis factor {alpha}-induced matrix metalloproteinase-9 expression in monocytes J. Leukoc. Biol., April 1, 2001; 69(4): 613 - 621. [Abstract] [Full Text]

				C. Chizzolini, R. Rezzonico, C. De Luca, D. Burger, and J.-M. Dayer Th2 Cell Membrane Factors in Association with IL-4 Enhance Matrix Metalloproteinase-1 (MMP-1) While Decreasing MMP-9 Production by Granulocyte-Macrophage Colony-Stimulating Factor-Differentiated Human Monocytes J. Immunol., June 1, 2000; 164(11): 5952 - 5960. [Abstract] [Full Text] [PDF]

				Y. Zhang, K. McCluskey, K. Fujii, and L. M. Wahl Differential Regulation of Monocyte Matrix Metalloproteinase and TIMP-1 Production by TNF-{alpha}, Granulocyte-Macrophage CSF, and IL-1{beta} Through Prostaglandin-Dependent and -Independent Mechanisms J. Immunol., September 15, 1998; 161(6): 3071 - 3076. [Abstract] [Full Text] [PDF]

				M. L. Corcoran, M. C. Kibbey, H. K. Kleinman, and L. M. Wahl Laminin SIKVAV Peptide Induction of Monocyte/Macrophage Prostaglandin E[IMAGE] and Matrix Metalloproteinases J. Biol. Chem., May 5, 1995; 270(18): 10365 - 10368. [Abstract] [Full Text] [PDF]

				H. Birkedal-Hansen, W.G.I. Moore, M.K. Bodden, L.J. Windsor, B. Birkedal-Hansen, A. DeCarlo, and J.A. Engler Matrix Metalloproteinases: A Review Critical Reviews in Oral Biology & Medicine, January 1, 1993; 4(2): 197 - 250. [Abstract] [Full Text] [PDF]