It is known that the PleioTropic Cytokine, Transforming Growth Factor-ß (TGF-ß) 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-ß1, -ß2, and -ß3 Isoforms, and TGF-ß Receptor type I (TGF-ßR-I) and TGF-ßR-II expression by ImmunoHistoChemistry on postmortem Brain tissue from MS and normal control cases.
To validate the TGF-ß staining results, we demonstrated that cultured human adult Astrocytes that produce biological active TGF-ß2, and to a lesser extent TGF-ß1, were ImmunoReactive for all 3 TGF-ß isoforms. Moreover, at mRNA level TGF-ß1 was detected in MS and normal control Brain tissue.
In normal control Brain tissue, TGF-ß isoforms were expressed in ramified Microglia and TGF-ß2, and -ß3 on Neuronal Cells in the Gray Matter TGF-ßR-I and TGF-ßR-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-ß Isoforms in PeriVascular and Parenchymal (foamy) Macrophages and in HyperTrophic Astrocytes.
Strong ImmunoReactivity for TGF-ßR-I and TGF-ßR-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-ß Isoforms and their Receptors were strongly expressed in HyperTrophic Astrocytes.
Our findings strongly suggest that the expression of the various TGF-ß 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.