Analysis of human blood monocyte activation at the level of gene expression. Expression of alpha interferon genes during activation of human monocytes by poly IC/LC and muramyl dipeptide.
Human monocytes were activated to secrete alpha interferon (IFN-alpha) by poly IC/LC but not by other monocyte activators, such as muramyl dipeptide (MDP). In contrast, monocytes were activated to secrete fibroblast growth factor (FGF) release by MDP but not by poly IC/LC. The amount of total RNA present in unactivated and activated human monocytes was similar. Using two 32P-labeled cDNA probes (pLM001 and HuIFN-alpha 2) for human IFN-alpha genes in hybridization studies, we analyzed messenger RNA species from this gene family in activated human monocytes. After activation with poly IC/LC, two other mRNA species (2.8 and 5.5 kb) were detected in addition to the 1.0 kb mRNA normally associated with IFN-alpha secretion. Unexpectedly, monocytes activated with MDP also contained 2.8 kb IFN-alpha mRNA. There was associated with this 2.8 kb IFN-alpha mRNA, found in MDP-activated monocytes, appreciable levels of intracellular IFN-alpha activity in the absence of detectable secreted IFN-alpha. Thus the secretion of IFN-alpha in activated human monocytes can be correlated with the appearance of a 1.0 kb mRNA species after poly IC/LC exposure. Secretion appears to be defective in MDP-stimulated monocytes even though they contain active intracellular IFN-alpha apparently translated from the 2.8 kb mRNA.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D002266:Carboxymethylcellulose Sodium / Q000494:pharmacology* / Q000031:analogs & derivatives; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000096:biosynthesis; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics*; D008262:Macrophage Activation; D008747:Methylcellulose / Q000031:analogs & derivatives*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D011070:Poly I-C / Q000494:pharmacology*; D011107:Polylysine / Q000494:pharmacology* / Q000031:analogs & derivatives; D012333:RNA, Messenger / Q000302:isolation & purification
D007370:Interferon Type I; D010455:Peptides; D012333:RNA, Messenger; D011107:Polylysine; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D005346:Fibroblast Growth Factors; C019531:poly ICLC; D008747:Methylcellulose; D004247:DNA; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C