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 substanti al phenotypic diversity, some of which relates to the capacity for cro ss-talk with cells of the immune system. We examine, for the first tim e, thyroid fibroblast biology in culture. Thyroid explants were placed in culture, and fibroblasts were outgrown and serially passaged. Thes e fibroblasts take on a morphology in culture resembling cells from ot her anatomic regions. When treated with PGE,, they assume a stellate m orphology similar to that of prostanoid-treated orbital fibroblasts. T he 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/m l) 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-kappa B binding activity is up-regulated as is interleukin (IL) -6 and IL-8 expression. IL-1 beta treatment up-regulates the expressio n of IL-1 alpha, IL-1 beta, and PGE,. These observations suggest that thyroid fibroblasts possess the molecular machinery necessary for cros s-talk with immunocompetent cells such as lymphocytes and mast cells t hrough the CD40/CD40L complex, as well as through classic cytokine net works, and to participate potentially in the inflammatory response of the thyroid gland.