PMID- 1377078
OWN - NLM
STAT- MEDLINE
DCOM- 19920724
LR  - 20190613
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 569
IP  - 1
DP  - 1992 Jan 8
TI  - Cooperative regulation of nerve growth factor synthesis and secretion in 
      fibroblasts and astrocytes by fibroblast growth factor and other cytokines.
PG  - 14-25
AB  - Acidic fibroblast growth factor (aFGF) enhances nerve growth factor (NGF) 
      synthesis by astrocytes obtained from various brain regions. NGF secretion by 
      fibrous-shaped astrocytes transformed by dibutyryl-cAMP (db-cAMP) pretreatment 
      was less than that by untreated astrocytes. However, aFGF also enhanced NGF 
      secretion by fibrous-shaped astrocytes. The effects of various kinds of 
      intracellular signaling modulators on NGF synthesis were examined. None of the 
      following second messenger effectors had an effect on NGF synthesis: protein 
      kinase C (PKC) agonist (phorbol myristate acetate (PMA)) or antagonist 
      (sphingosine (SP)). LiCl, and ionomycin (Iono). Further, increases of 
      intracellular cAMP by forskolin (FK) or db-cAMP have no significant effect on NGF 
      synthesis in astrocytes under a standard culture condition. However, NGF 
      synthesis by astrocytes in the presence of aFGF was significantly enhanced by 
      db-cAMP, but not by FK or sodium butyrate. These results indicate that an 
      excessive amount of cAMP enhances the effect of aFGF on NGF synthesis in 
      astrocytes. NGF synthesis in astrocytes was not affected by treatment with 
      anti-aFGF or anti-bFGF neutralizing antibodies, indicating that FGFs are not 
      involved in the autocrine regulation of NGF synthesis in astrocytes. Transforming 
      growth factor-beta 1 (TGF-beta 1), which inhibits some effects of FGFs, increased 
      NGF synthesis in concert with aFGF. Furthermore, the highest NGF synthesis was 
      observed when astrocytes were stimulated by all of the following cytokines: aFGF, 
      interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and 
      TGF-beta 1. The mechanism regulating NGF synthesis in fibroblasts obtained from 
      prenatal rat skin was also investigated. Acidic FGF, basic FGF (bFGF), epidermal 
      growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth 
      factor-alpha (TGF-alpha), TGF-beta 1, IL-1 beta, and TNF-alpha were found to be 
      regulators of NGF synthesis in skin fibroblasts. Among these cytokines, aFGF is 
      the most potent regulator of NGF synthesis in fibroblasts. NGF synthesis by skin 
      fibroblasts, either in the presence or absence of aFGF, was not modified by any 
      of the following: FK, PMA, SP, LiCl, and Iono. However, db-cAMP significantly 
      enhanced NGF synthesis in both conditions. Sodium butyrate enhanced NGF synthesis 
      in the presence of aFGF, but not in the absence of aFGF. These results suggest 
      that an excessive amount of cAMP and butyrate moiety regulate NGF synthesis in 
      skin fibroblasts in different ways.(ABSTRACT TRUNCATED AT 400 WORDS)
FAU - Yoshida, K
AU  - Yoshida K
AD  - Department of Neurosciences, School of Medicine, University of California, San 
      Diego, La Jolla 92123.
FAU - Gage, F H
AU  - Gage FH
LA  - eng
GR  - AG 06088/AG/NIA NIH HHS/United States
GR  - AG 08514/AG/NIA NIH HHS/United States
GR  - NS 28121/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Cytokines)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Fibroblast Growth Factor)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 104781-85-3 (Fibroblast Growth Factor 1)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 63X7MBT2LQ (Bucladesine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Newborn
MH  - Astrocytes/drug effects/*metabolism
MH  - Brain/*metabolism
MH  - Bucladesine/pharmacology
MH  - Cytokines/*pharmacology
MH  - Epidermal Growth Factor/pharmacology
MH  - Fetus
MH  - Fibroblast Growth Factor 1/metabolism/*pharmacology
MH  - Fibroblast Growth Factor 2/metabolism/*pharmacology
MH  - Fibroblasts/drug effects/metabolism
MH  - Kinetics
MH  - Nerve Growth Factors/*biosynthesis/metabolism
MH  - Organ Specificity
MH  - Rats
MH  - Rats, Inbred F344
MH  - Receptors, Cell Surface/metabolism
MH  - Receptors, Fibroblast Growth Factor
MH  - Recombinant Proteins/pharmacology
MH  - Skin/drug effects/*metabolism
MH  - Transforming Growth Factor beta/pharmacology
EDAT- 1992/01/08 00:00
MHDA- 1992/01/08 00:01
CRDT- 1992/01/08 00:00
PHST- 1992/01/08 00:00 [pubmed]
PHST- 1992/01/08 00:01 [medline]
PHST- 1992/01/08 00:00 [entrez]
AID - 0006-8993(92)90364-F [pii]
AID - 10.1016/0006-8993(92)90364-f [doi]
PST - ppublish
SO  - Brain Res. 1992 Jan 8;569(1):14-25. doi: 10.1016/0006-8993(92)90364-f.