Caco-2 cells express type I interleukin-1 receptors: ligand binding enhances proliferation.
We examined the effect of interleukin-1 (IL-1) on the rate of proliferation of the human colon carcinoma Caco-2 and characterized the human intestinal epithelial cell IL-1 receptor (IL-1R). IL-1 dose dependently increased tritiated thymidine uptake in confluent Caco-2 monolayers fed complete growth medium. An anti-IL-1 beta completely blocked the increase in tritiated thymidine uptake, whereas an IL-1 receptor antagonist human recombinant blocked it partially. In long-term culture, IL-1 increased DNA content over control, an effect similar to that of epidermal growth factor (EGF). Unlike EGF, IL-1 did not enhance tritiated thymidine uptake in Caco-2 monolayers grown in serum-free medium, implying that IL-1 needs a cofactor(s) to elicit its proliferative effect. Cross-linking 125I-IL-1 beta to Caco-2 membranes revealed a binding protein of approximately 80 kDa with binding saturated at approximately 2.5 x 10(9) M-1 consistent with that for the type I IL-1R. cDNA transcribed from Caco-2 mRNA and amplified by polymerase chain reaction, using complementary oligonucleotides, resulted in a reaction product matching the sequence of the type I IL-1R. Our results demonstrate that IL-1 enhances proliferation of Caco-2 cells. This effect requires the presence of an unidentified cofactor(s). Also, Caco-2 cells express the type I IL-1R.
Varilek
G W
GW
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, 52242.
Neil
G A
GA
Bishop
W P
WP
D000345:Affinity Labels / Q000378:metabolism; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D007422:Intestines / Q000737:chemistry* / Q000166:cytology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D017472:Receptors, Interleukin-1 / Q000032:analysis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000345:Affinity Labels; D003470:Culture Media; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins