Renal fibroblasts are sensitive to growth-repressing and matrix-reducing factors from activated lymphocytes.
Various forms of nephropathy accompany interstitial fibrosis with lymphocytic infiltration. To probe the relationship between lymphocyte-derived factors and renal fibroblasts, we studied the effect of culture supernatant from lymphocytes stimulated by concanavalin A (ConASN) on the growth and matrix metabolism of rat kidney fibroblasts. 3H-thymidine incorporation and Northern analysis, respectively, revealed that ConASN repressed cell growth and the mRNA level of collagen type I, but dramatically elevated the steady-state expression of metalloproteinase transin/stromelysin. The growth inhibitor in ConASN was moderately heat-sensitive and less than 5 kD in molecular size, qualities that differed from those of transforming growth factor-beta (TGF-beta), IL-1 beta, IL-6, and tumour necrosis factor-alpha (TNF-alpha). The matrix regulatory factor in ConASN was highly heat-sensitive and more than 30 kD in size. Among several lymphokines tested, TNF-alpha produced the same effects as ConASN on the metabolism of extracellular matrix. We hypothesize that lymphocyte-derived factors have a significant role in the attenuation of renal fibrogenesis, as well as its progression, via inhibiting cell growth and matrix accumulation.
Kitamura
A
A
Department of Internal Medicine, Saitama Medical Center, Japan.
Kitamura
M
M
Nagasawa
R
R
Maruyama
N
N
Mitarai
T
T
Takahashi
T
T
Isoda
K
K
D000818:Animals; D001685:Biological Factors / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003470:Culture Media; D005109:Extracellular Matrix / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors*; D005347:Fibroblasts / Q000276:immunology; D007668:Kidney / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000276:immunology; D008297:Male; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D008970:Molecular Weight; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D001685:Biological Factors; D003470:Culture Media; D008222:Lymphokines; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D003094:Collagen; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3