Tumor necrosis factor is markedly synergistic with interleukin 1 and interferon-gamma in stimulating the production of nerve growth factor in fibroblasts.
A possible interaction between tumor necrosis factor-alpha (TNF) and other cytokines/growth factors in stimulating the production of nerve growth factor (NGF) in Swiss 3T3 cells was studied. TNF's stimulatory activity on fibroblast NGF production was synergized by interleukin-1 alpha (IL-1 alpha), IL-1 beta and interferon-gamma (IFN-gamma), but was antagonized by transforming growth factor-beta (TGF-beta). The most remarkable synergistic effect was observed between TNF and IL-1 alpha/beta; as little as 0.003 ng/ml of IL-1 beta markedly enhanced TNF's stimulatory activity on NGF production in the cells. These findings reinforce the idea that TNF, in concert with IL-1 alpha/beta, plays an essential role in regulating the regeneration of peripheral nerves following injury through an indirect mechanism by which it stimulates NGF production in fibroblasts.
Hattori
A
A
Department of Biology, Gifu Pharmaceutical University, Japan.
Iwasaki
S
S
Murase
K
K
Tsujimoto
M
M
Sato
M
M
Hayashi
K
K
Kohno
M
M
D016475:3T3 Cells; D000818:Animals; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D007375:Interleukin-1 / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D007375:Interleukin-1; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma