The effects of antisense insulin-like growth factor-I receptor oligonucleotide on human cord blood lymphocytes

Abstract

Our objective was to study the effects of type I insulin-like growth factor receptor (IGF-IR) on human cord blood lymphocyte (CBL) functions. First, we used RT-PCR to determine the expression of IGF-IR at the mRNA level in CBL. We then inhibited the expression of IGF-IR in CBL by the antisense oligonucleotide for the IGF-IR gene. We measured the changes in interleukin (IL)-2, -4 and interferon-gamma (IFN gamma) at mRNA levels by RT-PCR, immunoglobulin M (IgM) production by CBL with an ELISA and lymphocyte proliferation by a (3)H-thymidine uptake technique. Our results showed that IGF-IR mRNA was detected in both non-activated and activated CBL, but the expression levels in the activated CBL were higher than those in the non-activated CBL. After being exposed to the antisense oligonucleotide, a 50% reduction in the amount of IGF-IR mRNA occurred. Accordingly, the proliferation of CBL to mitogen was significantly reduced about 50%, and the production of IgM from CBL was also markedly decreased. In the phytohemagglutinin-stimulated CBL culture system, when the IGF-IR antisense oligonucleotide existed, the mRNA levels of IFN gamma and IL-2 decreased 30-50% and IL-4 decreased 20-30%. We concluded that IGF-IR is most likely involved in the process of CBL proliferation and production of immunoglobulin and cytokines. It might therefore play an important role in the modulation of the immune functions.