The effects of antisense insulin-like growth factor-I receptor oligonucleotide on human cord blood lymphocytes.
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.
Yang
Y
Y
Pediatrics Institute, Children's Hospital, Shanghai Medical University, 183 Feng Lin Road, Shanghai 200032, China. yyang@shmu.edu.cn
Niu
J
J
Guo
L
L
D001483:Base Sequence; D005312:Fetal Blood / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics*
D007075:Immunoglobulin M; D007376:Interleukin-2; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D017526:Receptor, IGF Type 1