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Expression of transforming growth factor (TGF)-β1, -β2, and -β3 isoforms and TGF-β type I and type II receptors in multiple sclerosis lesions and human adult astrocyte cultures

被引：104
作者：
De Groot, CJA
Montagne, L
Barten, AD
Sminia, P
Van der Valk, P
机构：
[1] Vrije Univ Amsterdam, Acad Hosp, Dept Pathol, Div Neuropathol, NL-1007 MB Amsterdam, Netherlands
[2] Grad Sch Neurosci, Amsterdam, Netherlands
[3] Univ Amsterdam, Acad Med Ctr, Dept Radiotherapy, NL-1105 AZ Amsterdam, Netherlands
来源：
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY | 1999年 / 58卷 / 02期
关键词：
cell cultures; hypertrophic astrocytes; immunohistochemistry; macrophages; microglia; multiple sclerosis; TGF-beta bioassay;
D O I：
10.1097/00005072-199902000-00007
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
It is known that the pleiotropic cytokine transforming growth factor beta (TGF-beta) has a regulatory role in the process of tissue repair and remodelling following injury. As reports on these molecules in multiple sclerosis (MS) lesion with different lesional activity are rare, we studied the cellular localization of TGF-beta 1, -beta 2, and -beta 3 isoforms, and TGF-beta receptor type I (TGF-beta R-I) and TGF-beta R-II expression by immunohistochemistry on postmortem brain tissue from MS and normal control cases. To validate the TGF-beta staining results we demonstrated that cultured human adult astrocytes that produce biological active TGF-beta 2, and to a lesser extent TGF-beta 1, were immunoreactive for all 3 TGF-beta isoforms. Moreover, at mRNA level TGF-beta 1 was detected in MS and normal control brain tissue. In normal control brain tissue, TGF-beta isoforms were expressed in ramified microglia and TGF-beta 2, and -beta 3 on neuronal cells in the gray matter. TGF-beta R-I and TGF-beta R-II expression was found on endothelial cells, astrocytes, microglia, and neurons. In active demyelinating MS lesions a strong to intense immunoreactivity was detected for all 3 TGF-beta isoforms in perivascular and parenchymal (foamy) macrophages and in hypertrophic astrocytes. Strong immunoreactivity for TGF-beta R-I and TGF-beta R-II was found on macrophages in both parenchymal and perivascular areas and on hypertrophic astrocytes and endothelial cells in active demyelinating MS lesions. In chronic active and inactive MS lesions, all 3 TGF-beta isoforms and their receptors were strongly expressed in hypertrophic astrocytes. Our findings strongly suggest that the expression of the various TGF-beta isoforms and their receptor types found in MS lesions with different cellular activity participate in reactive processes leading to the formation of chronic MS lesions.
引用
收藏
页码：174 / 187
页数：14
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