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

Cell Signal. 2003 Aug;15(8):793-802. doi: 10.1016/s0898-6568(03)00039-1.


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.

MeSH terms

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


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