title: Biphasic increase in circulating and renal TNF-alpha in MRL-lpr mice with differing regulatory mechanisms.
abstract: Tumor necrosis factor (TNF)-alpha contributes to expansion of lymphocytes in neonatal mice and can accelerate renal injury. T cells induced by the lpr gene promote renal injury. However, the lpr gene alone is insufficient to cause renal damage, since MRL-lpr, but not C3H-lpr mice develop lupus nephritis. In this study, we examined the temporal expression of TNF-alpha in the kidney and circulation of mice (MRL and C3H) with the lpr gene and their congenic counterparts (++). We measured a bioactive TNF-alpha using L929 cells and tissue expression with an avidin-biotin immunoperoxidase method. A biphasic increase in circulating TNF-alpha in MRL-lpr mice was detected. There was an initial peak in neonatal mice (703 +- 208 pg/ml) which normalized by two months of age (87 +- 13 pg/ml) and reascended proportional to the severity of renal injury (non-proteinuric 570 +/- 87, proteinuric; 1255 +/- 135 pg/ml). In addition, there was only a single peak in neonatal C3H-lpr mice (1270 +/- 318 pg/ml) with a nadir by six weeks of age (434 +/- 52 pg/ml). In contrast, serum TNF-alpha was low in MRL-(++) and C3H-(++) mice (80 +/- 3 and 95 +/- 30 pg/ml), respectively. TNF-alpha expression in kidneys paralleled the serum pattern in MRL-lpr mice. Enhanced TNF-alpha expression was restricted to tubular epithelial cells (TEC) in neonatal MRL-lpr and C3H-lpr mice, and not detected in congenics. In adult mice, intrarenal TNF-alpha expression was more ubiquitous and was detected in glomeruli, vascular smooth muscle and perivascular infiltrating cells as well as TEC.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: H
authors.initials: H
authors.lastname: Yokoyama
authors.forename: B
authors.initials: B
authors.lastname: Kreft
authors.forename: V R
authors.initials: VR
authors.lastname: Kelley
mesh_terms: D000818:Animals; D015551:Autoimmunity; D002460:Cell Line; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha