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Mechanism of Regulation of Complement Receptor Type 1 Transcription by Cytosine Arabinoside in a Pre‐Erythroid Model
Author(s) -
T A Funkhouser,
D P Vik
Publication year - 1999
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1999.00454.x
Subject(s) - transcription (linguistics) , biology , protein kinase c , cytosine , microbiology and biotechnology , messenger rna , transcription factor , tyrosine kinase , receptor , dna , kinase , signal transduction , gene , biochemistry , philosophy , linguistics
Binding to erythrocyte complement receptor type 1 (CR1) clears immune complexes from blood and tissues, preventing complement‐mediated pathological inflammation in disease. Previous work has demonstrated that Ara‐C, a cytosine analogue, induces an 11‐fold increase in CR1 mRNA expression in K‐562 erythroleukaemia cells. In this work we therefore investigated whether the Ara‐C/K‐562 system could be used as a model for studying the pre‐erythroid regulation of CR1. We demonstrated that increased CR1 expression could be induced independently of increased haemoglobin expression. Increases in CR1 mRNA levels produced by Ara‐C treatment were not a function of increased stability of the message. However, Ara‐C induced a protein synthesis‐dependent increase in transcription initiation rate as early as 12 h after treatment. Further data suggest that the effect of Ara‐C on transcription is not a result of its direct DNA‐damaging or DNA polymerase‐inhibition activities. Induction of receptor transcription was inhibited by tyrosine kinase (TK) and protein kinase C (PKC) inhibitors. These data suggest that TK, PKC and dCTP‐adducted phospholipid signalling pathways may all play a role in the mechanism of Ara‐C‐induced CR1 transcription.