Thymosin-alpha1 regulates MHC class I expression in FRTL-5 cells at transcriptional level.
In this study we examined the effect of the synthetic peptide thymosin-alpha1 (T(alpha)1) on MHC class I expression in FRTL-5 cells. Treatment with T(alpha)1 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 T(alpha)1 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 Talpha1 on the regulation of gene expression at the molecular level, and may further contribute to explaining the results obtained using Talpha1 in the control of infectious diseases and tumor growth.
Giuliani
C
C
Chair of Endocrinology, University of Chieti, Italy.
Napolitano
G
G
Mastino
A
A
Di Vincenzo
S
S
D'Agostini
C
C
Grelli
S
S
Bucci
I
I
Singer
D S
DS
Kohn
L D
LD
Monaco
F
F
Garaci
E
E
Favalli
C
C
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D051921:Fos-Related Antigen-2; D005786:Gene Expression Regulation / Q000187:drug effects; D005805:Genes, MHC Class I / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008285:Major Histocompatibility Complex; D051379:Mice; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013552:Swine; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497872:FOSL2 protein, human; D051921:Fos-Related Antigen-2; C497873:Fosl2 protein, mouse; C497874:Fosl2 protein, rat; D016328:NF-kappa B; C075396:PD1 protein, pig; D012333:RNA, Messenger; D014157:Transcription Factors; D013947:Thymosin; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase; D000077596:Thymalfasin