Cytokines in human renal interstitial fibrosis. I. Interleukin-1 is a paracrine growth factor for cultured fibrosis-derived kidney fibroblasts.
We studied the role of interleukin-1 beta (IL-1 beta) and basic fibroblast growth factor (bFGF) in the proliferative response of transformed human renal interstitial fibroblast cell lines established from either a kidney with glomerulonephritis and interstitial fibrosis or a normal kidney in comparison to primary human foreskin fibroblasts. Growth of fibrosis-derived renal fibroblasts was inhibited in the presence of IL-1 receptor antagonist (IL-1Ra) by 35% (P < 0.005), suggesting that these cells produce IL-1 and possess IL-1 receptors as part of paracrine growth. In contrast, spontaneous proliferation of fibroblasts derived from a normal kidney or normal skin were not inhibited by IL-1Ra. In fibrosis-derived but not in normal renal cells, fibronectin synthesis was increased 2.2-fold (P < 0.01) in the presence of IL-1Ra. Addition of exogenous IL-1 beta or bFGF stimulated proliferation of skin fibroblasts. In contrast, growth of fibrosis-derived renal fibroblasts was stimulated by IL-1 beta and unchanged by bFGF. Growth of normal kidney fibroblasts was unaffected by bFGF and inhibited by IL-1 beta. We conclude that compared to normal fibroblasts, fibrosis-derived renal fibroblasts have a different cytokine-response profile, are IL-1-dependent, produce IL-1 as a paracrine growth factor and do not proliferate to bFGF, a classical fibroblast growth factor.
Lonnemann
G
G
Department of Medicine, New England Medical Center Hospital, Boston, Massachusetts, USA.
Shapiro
L
L
Engler-Blum
G
G
Müller
G A
GA
Koch
K M
KM
Dinarello
C A
CA
D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005353:Fibronectins / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D011863:Radioimmunoassay; D012795:Sialoglycoproteins / Q000494:pharmacology; D012867:Skin / Q000166:cytology
D005353:Fibronectins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins