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

被引:16
作者
Giuliani, C
Napolitano, G
Mastino, A
Di Vincenzo, S
D'Agostini, C
Grelli, S
Bucci, I
Singer, DS
Kohn, LD
Monaco, F
Garaci, E
Favalli, C
机构
[1] Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, I-00133 Rome, Italy
[2] Univ G dAnnunzio, Chair Endocrinol, Chieti, Italy
[3] Univ Messina, Fac Sci, Inst Microbiol, Messina, Italy
[4] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA
[5] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA
关键词
MHC class I; thymic factor; NF-kappa B; immunomodulators; gene regulation;
D O I
10.1002/1521-4141(200003)30:3<778::AID-IMMU778>3.0.CO;2-I
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In this study we examined the effect of the synthetic peptide thymosin-alpha 1 (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 1 gene (PD1). An increase in the expression of MHC class 1 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 T alpha 1 on the regulation of gene expression at the molecular level, and may further contribute to explaining the results obtained using T alpha 1 in the control of infectious diseases and tumor growth.
引用
收藏
页码:778 / 786
页数:9
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