The expression of acidic fibroblast growth factor (heparin-binding growth factor-1) and cytokine genes in human cardiac allografts and T cells.
The purpose of this study was to investigate the role of cytokines and growth factors in cardiac allograft rejection and vasculopathy (CAV). The polymerase chain reaction (PCR) was used to detect the expression of IL-1, IL-2, IL-4, IL-5, IL-6, TNF-alpha, IFN-gamma, TGF-beta, TCR-beta chain and aFGF genes in 21 myocardial biopsies obtained from 9 heart transplant patients. There was no statistically significant correlation between cytokine gene expression and rejection, although a trend toward increased IL-6 and TGF-beta expression was noted with rejection (6 of 10 biopsies with vs. 1 of 7 without rejection, and 4 of 9 biopsies with vs. none of 7 without rejection, respectively). IL-2 gene expression was detected in only 2 of 21 biopsies, both positive for rejection. IL-1, IL-4, IL-5, CD8, IFN-gamma, and TNF-alpha were not detected in any of the biopsies. TCR-beta chain mRNA was found in all biopsies, indicating the invariable presence of T cells regardless of histologic diagnosis of rejection. The aFGF gene was expressed in the majority (18 of 21) of biopsies, and its presence was not correlated with rejection. In addition to mRNA for the complete coding sequence of aFGF, two alternatively spliced mRNAs for aFGF were present in myocardial biopsies. Because aFGF and TCR beta genes were expressed in most biopsies, we determined whether aFGF mRNA was expressed in T cells; aFGF transcripts were found in 2 of 5 T-cell clones examined. Thus, aFGF mRNA in cardiac allografts may have been induced within the myocardium or elaborated by infiltrating T cells. The presence of mRNA for aFGF, a potent endothelial and smooth muscle cell mitogen, in allograft myocardium suggests that aFGF may play a role in the pathogenesis of CAV.
Zhao
X M
XM
Vanderbilt Transplant Center, Department of Thoracic Surgery, Nashville, Tennessee.
Yeoh
T K
TK
Hiebert
M
M
Frist
W H
WH
Miller
G G
GG
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics*; D016220:Fibroblast Growth Factor 1 / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014158:Transcription, Genetic; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000209:etiology
D016207:Cytokines; D016220:Fibroblast Growth Factor 1