Expression of alternatively spliced interleukin-1 receptor accessory protein mRNAs is differentially regulated during inflammation and apoptosis.

Abstract

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.

• Authors: Liselotte E Jensen, Alexander S Whitehead
• Journal: Cellular signalling (Cell Signal) Vol. 15 Issue 8 Pg. 793-802 (Aug 2003) ISSN: 0898-6568 [Print] England
• PMID: 12781872 (Publication Type: Journal Article)

Chemical References

• IL1RAP protein, human
• Interleukin-1
• Interleukin-1 Receptor Accessory Protein
• Phorbol Esters
• Protein Isoforms
• Proteins
• RNA, Messenger
• Staurosporine

Topics

• Alternative Splicing (genetics)
• Apoptosis (genetics, immunology)
• Down-Regulation (drug effects, genetics, immunology)
• Humans
• Inflammation (genetics, immunology)
• Interleukin-1 (metabolism)
• Interleukin-1 Receptor Accessory Protein
• Molecular Sequence Data
• Phorbol Esters (pharmacology)
• Protein Isoforms (genetics, isolation & purification, metabolism)
• Protein Structure, Tertiary (genetics)
• Proteins (genetics)
• RNA, Messenger (drug effects, metabolism)
• Sequence Homology, Amino Acid
• Sequence Homology, Nucleic Acid
• Staurosporine (pharmacology)
• Stress, Physiological (genetics, immunology)
• Tumor Cells, Cultured