Immunohistochemical expression of growth factors in subacute thyroiditis and their effects on thyroid folliculogenesis and angiogenesis in collagen gel matrix culture

The inflammatory-mechanistic basis of subacute thyroiditis remains unclear. To elucidate the roles of vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (P DGF), transforming growth factor-beta 1 (TGF-beta 1) and epidermal growth f actor (EGF) in the inflammatory process, their immunoexpression was examine d in biopsy specimens of ten cases. At the granulomatous stage, all cases e xpressed VEGF, bFGF, PDGF, and TGF-beta 1 in monocytes/macrophages infiltra ting into follicle lumina, and in both epithelioid histiocytes and multinuc leated giant cells of the granulomas. In fibroblasts and endothelial cells around the granulomas, all cases displayed VEGF, bFGF, and PDGF, but TGF-be ta 1 was detected only in fibroblasts in two cases. No cases expressed EGF in any of the above cell types. At the regenerative stage, all cases expres sed VEGF, bFGF, and EGF in regenerating thyrocytes, whereas three and no ca ses displayed PDGF and TGF-beta 1, respectively. Ten, seven and six cases e xpressed PDGF in fibroblasts, endothelial cells, and monocytes, respectivel y. In these cell types, all cases expressed VEGF and bFGF, whereas no cases displayed TGF-beta 1 and EGF. To estimate the roles of these growth factor s in thyroid tissue regeneration, their effects on thyroid folliculogenesis and angiogenesis were examined using collagen gel culture of thyrocytes an d endothelial cells, respectively. Cell proliferation was also studied by b romodeoxyuridine (BrdU) uptake. EGF decreased follicle formation and TGF-be ta 1 drastically inhibited it, but the others had no effect. VEGF showed th e greatest effect on vessel formation, although all of the others promoted it. EGF and VEGF or bFGF caused the highest BrdU uptake in thyrocytes and e ndothelial cells, respectively. The data suggest firstly, that at the granu lomatous stage of subacute thyroiditis, growth factor-rich monocytes/macrop hages infiltrating into follicle lumina trigger the granulomatous reaction, and VEGF, bFGF, PDGF, and TGF-beta 1 produced by the stromal cell types te sted mediate the reaction; secondly, that at the regenerative stage, EGF se rves follicle regeneration through its mitogenic effect on thyrocytes, alth ough some cofactors with EGF are involved in folliculogenesis and the decre ased expression of TGF-beta 1, a fibrogenic factor, contributes to thyroid tissue repair; and thirdly, that VEGF and bFGF are more responsible for the angiogenesis at both stages than the other factors studied. Copyright (C) 1999 John Wiley & Sons, Ltd.