Synthesis of basic fibroblast growth factor by murine mast cells. Regulation by transforming growth factor beta, tumor necrosis factor alpha, and stem cell factor.
BACKGROUND
Mast cells (MC) are involved in a wide spectrum of disorders characterized by neovascularization and fibroproliferation. We and others recently reported that human MC are a source of basic fibroblast growth factor (b FGF-2), a potent angiogenic and mitogenic polypeptide, in several disease conditions, such as chronic inflammation, hemangioma, and benign cutaneous mastocytosis. These findings suggest that FGF-2 may be an important mediator of cell proliferation and angiogenesis associated with MC. Since MC are heterogeneous across species, it is unknown whether FGF-2 expression is a feature common to all MC, or whether FGF-2 expression by MC can be regulated. We therefore examined FGF-2 expression by MC in mouse tissue and MC lines.


METHODS
Immunostaining, RT-PCR, ELISA, immunoblot and Northern blot analyses were employed to study four murine MC lines for FGF-2 expression and its regulation by transforming growth factor-beta (TGF-beta), stem cell factor (SCF), and tumor necrosis factor-alpha (TNF-alpha).


RESULTS
Mouse tissue MC and three of four murine MC lines (CFTL-12, CFTL-15, ABFTL-3) express FGF-2 as judged by immunostaining, ELISA, Western blot and Northern blot analyses, and reverse transcription-polymerase chain reaction. While TNF-alpha appeared to downregulate FGF-2 mRNA levels, treatment with SCF or TGF-beta resulted in an increase in the expression of FGF-2 at mRNA level which can be attenuated by TNF-alpha. However, the concurrent increase in FGF-2 protein was negligible, possibly due to immaturity of these cell lines.


CONCLUSIONS
Expression of FGF-2 may be a ubiquitous feature of MC in other species in addition to humans, and can be selectively regulated by SCF, TGF-beta and TNF-alpha.
Qu
Z
Z
Department of Medicine, Oregon Health Sciences University, Casey Eye Institute, Portland, USA.
Huang
X
X
Ahmadi
P
P
Stenberg
P
P
Liebler
J M
JM
Le
A C
AC
Planck
S R
SR
Rosenbaum
J T
JT
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D015536:Down-Regulation; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D007150:Immunohistochemistry; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D019089:Stem Cell Factor / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D012333:RNA, Messenger; D019089:Stem Cell Factor; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2