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.