Expression of alternatively spliced interleukin-1 receptor accessory protein mRNAs is differentially regulated during inflammation and apoptosis.
Two alternative splice variants of the interleukin-1 receptor accessory protein (IL-1RAcP) mRNA are known. Membrane-bound IL-1RAcP (mIL-1RAcP) promotes intracellular interleukin-1 (IL-1) signalling whereas soluble IL-1RAcP (sIL-1RAcP) is probably an inhibitor of IL-1 signalling. Here we establish that sIL-1RAcP mRNA levels increase 16-fold in response to phorbol esters in the human hepatoma cell line HepG2 via a mechanism that depends on de novo protein synthesis. Following exposure of cells to UV light, a potent inducer of apoptosis, mIL-1RAcP mRNA is rapidly down-regulated and a new steady-state level established briefly before a gradual return to pretreatment levels. Following treatment with staurosporine, also an inducer of apoptosis, mIL-1RAcP mRNA levels steadily decrease through 72 h, with little change in sIL-1RAcP mRNA levels. A novel alternative splice variant, sIL-1RAcP-beta, was identified. Its sequence indicates that sIL-1RAcP-beta is secreted and has a unique second half of the third immunoglobulin (Ig) domain. The dramatic changes in levels of IL-1RAcP mRNAs suggest important functions in regulating sensitivity to IL-1 during stress and may play a role in oncogenic processes that are engaged during chronic inflammation.
Jensen
Liselotte E
LE
Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania, 156 Johnson Pavilion, 3620 Hamilton Walk, Philadelphia, PA 19104, USA. jensen@pharm.med.upenn.edu
Whitehead
Alexander S
AS
D017398:Alternative Splicing / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics* / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism; D053577:Interleukin-1 Receptor Accessory Protein; D008969:Molecular Sequence Data; D010703:Phorbol Esters / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D019311:Staurosporine / Q000494:pharmacology; D013312:Stress, Physiological / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured
C507765:IL1RAP protein, human; D007375:Interleukin-1; D053577:Interleukin-1 Receptor Accessory Protein; D010703:Phorbol Esters; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; D019311:Staurosporine