[Analysis of the regulation of HLA class II genes by forskolin].
The expression of HLA class II molecules is mainly regulated transcriptionally and this regulation is thought to play an important role to the control of immune response. In this report, we have studied the effect of adenylate cyclase activator, forskolin, to the expression of HLA class II molecules on the cell surface of an human multiple myeloma cell line, RPMI8226. On the northern blot analysis and FACS analysis, we have revealed that forskolin upregulated the expression of mRNAs of DQB and DRB gene and their products on its surface. On the sequence analysis of upstream of HLA-DQB gene, we have identified not only Y-,X-, W-box, which were thought to regulatory region of truncated gene, but also cAMP responsible element (CRE) like regulatory region, which located upstream of W-box. On the gel retardation assay, when we used DNA probes that were specific for CRE like region and Y-box, we have found newly detectable bands, which appeared by forskolin treatment. These data suggest that forskolin upregulates HLA class II molecules by means of the interaction between CRE and cAMP responsible element binding protein (CREB).
Shibata
T
T
Second Department of Pathology, Asahikawa Medical College, Japan.
Kawabata
I
I
Katagiri
M
M
D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D005576:Colforsin; D000242:Cyclic AMP