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Originally published In Press as doi:10.1074/jbc.M206007200 on September 10, 2002

J. Biol. Chem., Vol. 277, Issue 46, 43757-43762, November 15, 2002
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NF-kappa B Activation Mediates the Cross-talk between Extracellular Matrix and Interferon-gamma (IFN-gamma ) Leading to Enhanced Monokine Induced by IFN-gamma (MIG) Expression in Macrophages*

Maureen R. HortonDagger §, Sada Boodoo§, and Jonathan D. Powell

From the § Departments of Medicine and  Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287

In intact tissue, the extracellular matrix (ECM) provides support and helps maintain homeostasis but is considered biologically inert. In the setting of inflammation, not only is the ECM the target of inflammation, but its breakdown products modulate the magnitude and quality of an immune response. Fragments of the ECM component hyaluronan (HA) induce macrophage expression of chemokines, cytokines, and growth factors as well greatly enhance IFN-gamma -induced MIG expression. In this report, we demonstrate that the synergistic induction of MIG by HA and IFN-gamma occurs at the level of transcription via NF-kappa B. Using electrophoretic mobility shift assays and reporter assays, we have identified two NF-kappa B sites proximal to the IFN-gamma -responsive element-1 (gamma RE-1) that mediate this effect. Interestingly, our experiments also revealed a critical role for NF-kappa B in mediating IFN-gamma -induced MIG expression independent of HA. These data emphasize the ability of "degraded self" to activate/modify immune responses through the NF-kappa B pathway.

* This work was supported by Grant K08 HL03993 from the National Institutes of Health and Grant RG-061-N from the American Lung Association.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: 600 North Wolfe St., Jefferson Bldg. B1-170, Baltimore, MD 21287. Tel.: 410-502-7037; Fax: 410-502-7048.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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