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Division of Molecular and Cellular Medicine, Department of Medicine (T.J.S., H.-S.W.), Department of Biochemistry and Molecular Biology (T.J.S., H.J.C.), Albany Medical College, Samuel S. Stratton Veterans Affairs Medical Center, Albany, New York 12208; the Cancer Center and Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry (G.D.S., R.P.P.), Rochester, New York 14642; and Infectious Disease Section, Department of Medicine, State University of New York at Buffalo (C.S.B.), Department of Veterans Affairs Medical Center, Buffalo, New York 14215
Address all correspondence and requests for reprints to: Terry J. Smith, M.D., Division of Molecular and Cellular Medicine (A-175), Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208.
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-
(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-
B binding activity is
up-regulated as is interleukin (IL)-6 and IL-8 expression. IL-1ß
treatment up-regulates the expression of IL-1
, IL-1ß, 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.
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T. J. Smith and S. J. Parikh HMC-1 Mast Cells Activate Human Orbital Fibroblasts in Coculture: Evidence for Up-Regulation of Prostaglandin E2 and Hyaluronan Synthesis Endocrinology, August 1, 1999; 140(8): 3518 - 3525. [Abstract] [Full Text]
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 T. J. Smith, T. A. Jennings, D. Sciaky, and H. J. Cao Prostaglandin-endoperoxide H Synthase-2 Expression in Human Thyroid Epithelium. EVIDENCE FOR CONSTITUTIVE EXPRESSION IN VIVO AND IN CULTURED KAT-50 CELLS J. Biol. Chem., May 28, 1999; 274(22): 15622 - 15632. [Abstract] [Full Text] [PDF]
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H. J. Cao, H.-S. Wang, Y. Zhang, H.-Y. Lin, R. P. Phipps, and T. J. Smith Activation of Human Orbital Fibroblasts through CD40 Engagement Results in a Dramatic Induction of Hyaluronan Synthesis and Prostaglandin Endoperoxide H Synthase-2 Expression. INSIGHTS INTO POTENTIAL PATHOGENIC MECHANISMS OF THYROID-ASSOCIATED OPHTHALMOPATHY J. Biol. Chem., November 6, 1998; 273(45): 29615 - 29625. [Abstract] [Full Text] [PDF]
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