Expression and synthesis of fibroblast growth factor-9 in human gammadelta T-lymphocytes. Response to isopentenyl pyrophosphate and TGF-beta1/IL-15.
Gammadelta T-lymphocytes are believed to play a role in maintaining the normal configuration of epithelial tissue. As little is known about the factors mediating this function, we addressed the question of whether gammadelta T-lymphocytes produce fibroblast growth factor (FGF)-9 as well as two other growth factors associated with epithelial tissue reconstitution. Blood gammadelta T cells isolated from healthy donors were grown in the presence of isopentenyl pyrophosphate (IPP) or transforming growth factor-beta1 (TGF-beta1)/interleukin-15 (IL-15) for 24 h and were assessed for the expression and synthesis of FGF-9, keratinocyte growth factor (KGF), and epidermal growth factor (EGF). Resting human gammadelta T cells constitutively expressed KGF and FGF-9 mRNA but no EGF mRNA. In the presence of IPP, FGF-9 mRNA expression significantly increased in a dose-dependent manner, expression of KGF remained unaltered, and EGF mRNA could not be detected. In contrast to IPP, stimulation of the cells with TGF-beta1/IL-15 did not alter FGF-9 expression. Moreover, stimulation with anti-CD3 does not induce FGF-9 expression but triggers a high signal of interferon-gamma mRNA. Western blot analysis of gammadelta T cell lysates, prepared 4 days following stimulation with IPP, showed an increase of FGF-9 protein as compared with control cells. In conclusion, the results demonstrate for the first time that human blood and bronchoalveolar lavage gammadelta T-lymphocytes are capable of expressing FGF-9. The data also provide novel evidence that immunoregulatory cells can synthesize FGF-9.
Workalemahu
Grefachew
G
University of Medical Clinic I, Department of Pnuemology and Allergy/Immunology, Friedrich-Schiller-University Jena, Jena, Germany. grefachew.workalemahu@med.uni-jena.de
Foerster
Martin
M
Kroegel
Claus
C
D015153:Blotting, Western; D017252:CD3 Complex / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000235:genetics; D051523:Fibroblast Growth Factor 7; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D045782:Hemiterpenes / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D019409:Interleukin-15 / Q000494:pharmacology*; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D017252:CD3 Complex; C496453:FGF7 protein, human; C496459:FGF9 protein, human; D051525:Fibroblast Growth Factor 9; D045782:Hemiterpenes; D019409:Interleukin-15; D009943:Organophosphorus Compounds; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D051523:Fibroblast Growth Factor 7; C004809:isopentenyl pyrophosphate; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D007371:Interferon-gamma