Increased tumor necrosis factor and IL-1 beta gene expression in the kidneys of mice with lupus nephritis.
Because TNF and IL-1 can initiate immunologic and inflammatory events alone or synergistically, a local increase in the levels of one or both of these cytokines in vivo may cause irreparable tissue damage. The purpose of this study was to evaluate local TNF and IL-1 beta gene expression in vivo in the kidneys of MRL-Ipr mice with autoimmune lupus nephritis. TNF mRNA was detected in the renal cortex of MRL-Ipr mice but was not present in the cortex of normal congenic MRL-++ or C3H/FeJ mice. MRL-Ipr mice with lupus nephritis expressed higher amounts of TNF mRNA compared with MRL-Ipr mice prior to disease. In addition, freshly isolated, unstimulated glomeruli from MRL-Ipr mice with nephritis were found to secrete detectable levels of TNF, whereas glomeruli from MRL-++ mice did not. IL-1 beta mRNA, present in the renal cortex of C3H/FeJ, MRL-++, and young MRL-Ipr mice with normal kidneys, was also more abundantly expressed in MRL-Ipr mice with nephritis. Cultured macrophages from glomeruli of mice with nephritis were found to express TNF and IL-1 beta mRNA and product. These macrophages are prominent only in MRL-Ipr mice with renal disease and are the likely source of increased gene expression for both cytokines.
Boswell
J M
JM
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Yui
M A
MA
Burt
D W
DW
Kelley
V E
VE
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D005796:Genes; D007375:Interleukin-1 / Q000235:genetics* / Q000302:isolation & purification; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000302:isolation & purification
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha