IL-6 stimulation of insulin-like growth factor binding protein (IGFBP)-1 production.
TNF alpha and IL-1 beta have previously been shown to increase the IGFBP-1 concentration in plasma and liver under in vivo conditions. The present study demonstrates that another inflammatory cytokine, IL-6, also elevates a 30- to 32-kDa IGF binding protein in the plasma of mice. Moreover, IL-6 produced dose- and time-dependent increases in IGFBP-1 production by HepG2 cells. The maximal IL-6-induced increase in IGFBP-1 was comparable to that observed with dexamethasone, and this increase was attenuated by diltiazem or dantrolene, both of which are known to reduce the cytosolic Ca2+ concentration. Finally, incubation of HepG2 cells with TNF alpha or IL-1 beta also increased IGFBP-1 in a dose-dependent manner. These results demonstrate that IGFBP-1 production is mediated directly by proinflammatory cytokines and suggest that this mechanism may be important for the upregulation of IGFBP-1 seen in catabolic conditions associated with overexpression of these cytokines.
Samstein
B
B
Department Surgery and Medicine/Endocrinology, State University of New York at Stony Brook 11794-8191, USA.
Hoimes
M L
ML
Fan
J
J
Frost
R A
RA
Gelato
M C
MC
Lang
C H
CH
D000818:Animals; D002460:Cell Line; D003620:Dantrolene / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000096:biosynthesis* / Q000097:blood; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004731:Endotoxins; D018970:Insulin-Like Growth Factor Binding Protein 1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004110:Diltiazem; D003620:Dantrolene