Human thyroid fibroblasts exhibit a distinctive phenotype in culture: characteristic ganglioside profile and functional CD40 expression.
Fibroblasts from different regions of the human body exhibit substantial phenotypic diversity, some of which relates to the capacity for cross-talk with cells of the immune system. We examine, for the first time, thyroid fibroblast biology in culture. Thyroid explants were placed in culture, and fibroblasts were outgrown and serially passaged. These fibroblasts take on a morphology in culture resembling cells from other anatomic regions. When treated with PGE2, they assume a stellate morphology similar to that of prostanoid-treated orbital fibroblasts. The ganglioside profile exhibited by these cells is distinct from that observed previously in orbital and dermal fibroblasts. They uniformly express Thy-1, a surface glycoprotein. Messenger RNA encoding CD40, a surface receptor found on bone marrow-derived cells, and CD40 protein were expressed constitutively at low levels. Interferon-gamma (500 U/ml) treatment for 48-72 h resulted in high levels of surface HLA-DR and CD40 display. When CD40 is engaged with CD40 ligand (CD40L), nuclear factor-kappaB binding activity is up-regulated as is interleukin (IL)-6 and IL-8 expression. IL-1beta treatment up-regulates the expression of IL-1alpha, IL-1beta, and PGE2. These observations suggest that thyroid fibroblasts possess the molecular machinery necessary for cross-talk with immunocompetent cells such as lymphocytes and mast cells through the CD40/CD40L complex, as well as through classic cytokine networks, and to participate potentially in the inflammatory response of the thyroid gland.
Smith
T J
TJ
Department of Medicine, Albany Medical College, Samuel S. Stratton Veterans Affairs Medical Center, New York 12208, USA.
Sempowski
G D
GD
Berenson
C S
CS
Cao
H J
HJ
Wang
H S
HS
Phipps
R P
RP
D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology; D005347:Fibroblasts / Q000502:physiology; D005732:Gangliosides / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
D019013:CD40 Antigens; D016207:Cytokines; D005732:Gangliosides; D006684:HLA-DR Antigens; D007375:Interleukin-1; D008024:Ligands; D016328:NF-kappa B; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D007371:Interferon-gamma; D015232:Dinoprostone