Thymosin-α1 regulates MHC class I expression in FRTL-5 cells at transcriptional level

Abstract

In this study we examined the effect of the synthetic peptide thymosin‐α1 (Tα1) on MHC class I expression in FRTL‐5 cells. Treatment with Tα1 increased expression of MHC class I surface molecules and mRNA, which reached its peak (153 ± 8 % of the control value) after 12 h. Chloramphenicol acetyltransferase (CAT) analysis, following transfection with a plasmid containing the regulatory sequence of MHC class I (or its deletion derivatives) with the CAT reporter gene, and electrophoretic mobility shift assay experiments demonstrated that the action of Tα1 was at the transcriptional level, and its mechanism of action is likely due to increased binding between the complex p50 / fra‐2 and the enhancer A sequence of the 5' flanking region of a swine class I gene (PD1). An increase in the expression of MHC class I surface molecules was also observed by flow cytometry in murine and human tumor cell lines and in primary cultures of human macrophages. This study shows for the first time an effect of Tα1 on the regulation of gene expression at the molecular level, and may further contribute to explaining the results obtained using Tα1 in the control of infectious diseases and tumor growth.

Characterization of two thymosins as immune-related genes in common carp (Cyprinus carpio L.)

“…Since 1994, ProTα has been reported to inhibit the replication of virus and the reproduction of cancer cells by inducing immune cells (Baxevanis et al, 1994(Baxevanis et al, , 1995Haritos et al, 1985;Romani et al, 2004). Thymosin α1, corresponding to the first 28 amino acid residues of ProTα, was reported to increase the expression of MHC I which presented endogenous peptides to cytotoxic T cells to kill the virally infected cells as well as some cancer cells (Giuliani et al, 2000). It was also reported that Thymosin α1 inhibited viral replication in hepatitis virus B-transfected HepG2 tumor cells (Moshier et al, 1996).…”

Transcriptional regulation of major histocompatibility complex class I gene by insulin and IGF-I in FRTL-5 thyroid cells

“…Thus, there is an increased expression of MHC class I and II molecules in pancreatic islet cells of patients with type 1 diabetes mellitus and in thyrocytes from patients with autoimmune thyroid diseases (Hanafusa et al 1983, Bottazzo et al 1985, Kohn et al 2000. The importance of MHC class I overexpression is suggested by the observation that MHC class I-deficient mice do not develop autoimmunity in different experimental models: systemic lupus erythematosus (SLE), diabetes and autoimmune blepharitis (Mozes et al 1993, Serreze et al 1994, Chan et al 1995, Singer et al 1999.…”

“…We hypothesized that hormonal suppression of class I levels might be a physiologic mechanism to preserve self-tolerance and prevent autoimmune thyroid disease in the face of the hormonal increase of thyroid-specific genes, which are potential autoantigens (Saji et al 1992a, 1992b, 1997, Giuliani et al 1995, Taniguchi et al 1998, Kohn et al 2000. Other growth factors and cytokines, such as transforming growth factor (TGF)-1, thymosin 1 and , -interferons, also regulate MHC class I expressions in thyroid cells (Saji et al 1992b, Grassadonia et al 2004.…”

Thymosin Apha 1–A Peptide Immune Modulator with a Broad Range of Clinical Applications

“…Ta1 has also been shown to increase expression of proteins on the surface of virally-infected or tumor cells, including those that mediate antigen presentation such as Major Histocompatibility (MHC) Class I, MHC Class II, and beta-2 microglobulin [36,63], as well as tumorspecific antigens [64,65]. Immune escape by virally-infected and tumor cells has been correlated with down-regulation of antigen-presenting molecules [66,67].…”