Hallmarks of chronic inflammation and tissue fibrosis are increased influx of activated inflammatory cells, mediator release, and increased turnover and production of the extracellular matrix (ECM). Recent evidence has suggested that fragments of the ECM component hyaluronan play a role in chronic inflammation by inducing macrophage expression of chemokines. Interferon-γ (IFN-γ), an important regulator of macrophage functions, has been shown to induce the C-X-C chemokines Mig and IP-10. These chemokines affect T-cell recruitment and inhibit angiogenesis. The purpose of this investigation was to determine the effect of hyaluronan (HA) on IFN-γ-induced Mig and IP-10 expression in mouse macrophages. We found a marked synergy between HA and IFN-γ on Mig and IP-10 mRNA and protein expression in mouse macrophages. This was most significant with Mig, which was not induced by HA alone. The synergy was specific for HA, was not dependent on new protein synthesis, was not mediated by tumor necrosis factor-α, was selective for Mig and IP-10, and occurred at the level of gene transcription. These data suggest that the ECM component HA may influence chronic inflammatory states by working in concert with IFN-γ to alter macrophage chemokine expression.
This work was supported by grants from the National Institutes of Health (K11HL02880, RO1HL60539, and 5F32HL09614-02) and 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.
