TNF alpha, IL-1 alpha and bFGF are implicated in the complex disease of GM-CSF transgenic mice.
Transgenic mice aberrantly expressing the granulocyte-macrophage colony stimulating factor (GM-CSF) gene develop an unusual syndrome of blindness, tissue damage and wasting which is associated with accumulations of hemopoietic cells. In order to further characterize this disease state, we have used messenger RNA detection techniques to show that the genes for tumor necrosis factor (TNF alpha), interleukin-1 alpha (IL-1 alpha) and basic fibroblast growth factor (bFGF) are expressed at abnormally high levels in both macrophages and granulocytes in transgenic mice. Furthermore, since these cell types also express the GM-CSF transgene, it is likely that they are autocrine stimulated by GM-CSF. These observations raise the possibilities that, first, the expression of tumor necrosis factor alpha, interleukin-1 alpha and basic fibroblast growth factor in hemopoietic cells is a direct consequence of their autostimulation by GM-CSF, and second, that these cytokines may be responsible for some aspects of the transgenic mouse disease.
Lang
R A
RA
Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Cuthbertson
R A
RA
Dunn
A R
AR
D000818:Animals; D005128:Eye Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D006098:Granulocytes / Q000378:metabolism / Q000473:pathology; D006133:Growth Substances / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013577:Syndrome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics
D006133:Growth Substances; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor