Cytokine-induced macrophage differentiation: a tale of 2 genes

Winston, Brent W.; Krein, Peter M.
December 1999
Clinical & Investigative Medicine;Dec99, Vol. 22 Issue 6, p236
Academic Journal
Macrophages are versatile cells found in every tissue in the body. They must perform a number of diverse cellular functions that allow them to kill invading microorganisms and neoplastic cells as well as produce growth factors involved in wound healing. Macrophages that develop these diverse functions arise from a common precursor. By a process of selective adaptation, the common precursor monocyte/macrophage differentiates into a distinctive macrophage with a different and specific phenotype, characterized by the expression of a specific set of gene products. The local environment plays a critical role in shaping or directing the pattern or pathway of macrophage differentiation. The authors have focused on 2 specific macrophage differentiation pathways in a murine bone marrow-derived macrophage model. One pathway is believed to play a role in wound repair and is characterized by the induction of insulin-like growth factor-1 (IGF-I). The second pathway is involved in macrophage cytocidal activation and is characterized by the induction of the inducible form of nitric oxide synthase (iNOS). The pleotropic cytokine tumour necrosis factor-Alpha (TNF-Alpha) appears to mediate macrophage differentiation along both of these pathways. Interferon-gamma (IFN-Gamma), however, appears to act as a molecular switch. In the presence of IFN-Gamma, stimulation of macrophages with TNF-Alpha results in macrophage differentiation along a pathway in which iNOS is expressed, whereas, in the absence of IFN-Gamma, stimulation of macrophages with TNF-Alpha results in differentiation along a pathway in which IGF-I is expressed. The authors focus on some of the molecular events involved in TNF-Alpha and IFN-Gamma signal transduction and the regulation of iNOS and IGF-I genes in macrophages.


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