Effect of tumor necrosis factor‐α and interferon‐γ on the growth of a human salivary gland cell line

Ava J. Wu; Regina H. Kurrasch; Joseph KatzPhilip C. FoxBruce J. BaumJane C. Atkinson

摘要

AbstractInterferon‐γ (IFN‐γ) is a product of activated T‐lymphocytes, and tumor necrosis factor‐α (TNF‐α) is a product of both lymphocytes and macrophages. These cell types are often present at sites of tissue damage secondary to chronic infection or autoimmune disease. The purpose of this study was to characterize the effects of TNF‐α and IFN‐γ on a human submandibular gland epithelial cell line (HSG). IFN‐γ caused a concentration‐dependent decrease in HSG cell growth (∼70% in 6 days). Conversely, TNF‐α alone had little effect on the growth of these cells. When these cytokines were added in combination (20 units/ml TNF‐α and 1,000 units/ml of IFN‐γ), there was a synergistic antiproliferative effect; no apparent cell growth was observed. The cytokine‐induced antiproliferative effect was reversible. After the apparent cessation of cell growth for 3–6 days, removal of the cytokines permitted complete growth recovery. Further, cells that recovered and exhibited growth patterns that were similar to control cells remained susceptible to the antiproliferative effects of the cytokines. Flow cytometry revealed that the percentage of cells in G0/G1 with the combination of cytokines was significantly increased by 24 h. The antiproliferative effect of IFN‐γ alone and that of IFN‐γ and TNF‐α in combination were blocked completely using an antibody to the IFN‐γ receptor. A hypothesized mechanism of tissue damage in autoimmune inflammatory disorders is via up‐regulation of cell surface markers such as intercellular adhesion molecule type I (ICAM‐1) and histocompatibility antigen HLA‐DR which can exacerbate the inflammatory process. Treatment of HSG cells with IFN‐γ, with or without TNF‐α, resulted in increased levels of ICAM‐1 and the acquisition of HLA‐DR expression. These aggregate data suggest that IFN‐γ alone can regulate the expression of cell surface markers involved in the inflammatory process as well as cause a potent yet reversible inhibition of HSG cell growth that is modulated by the presence of TNF‐α. © 1994 Wiley‐Liss, Inc.This article is a US Governmen

Effect of tumor necrosis factor‐α and interferon‐γ on the growth of a human salivary gland cell line

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