Expression of membrane interleukin 1 by fibroblasts transfected with murine pro-interleukin 1 alpha cDNA.
Studies of interleukin 1 (IL-1) alpha and beta have emphasized their functional similarities. IL-1 alpha and -beta are encoded by ancestrally related genes that have diverged dramatically in primary sequence; however, only modest differences in the regulation or biological activity of IL-1 alpha and IL-1 beta have been documented. Here we show that mouse L cells transfected with murine pro-IL-1 alpha cDNA expressed biologically active, 33-kilodalton pro-IL-1 alpha, and that this pro molecule was neither processed to the 17-kilodalton mature form nor secreted. The transfected cells also expressed membrane-associated IL-1 biological activity, indicating that the pro-IL-1 alpha cDNA can direct expression of membrane-associated IL-1 and that cleavage of the pro molecule is not required for membrane presentation. In contrast, transfection of pro-IL-1 beta cDNA did not generate biologically active material in L cells. Evidence is presented that the native murine IL-1 beta precursor molecule is also biologically inactive in peritoneal exudate cells stimulated with lipopolysaccharide. These differences in distribution of the bioactive forms of IL-1 alpha and IL-1 beta may provide selective advantages for the maintenance of two gene products with similar functions.
Fuhlbrigge
R C
RC
Department of Pathology, Washington University School of Medicine, Saint Louis, MO 63110.
Fine
S M
SM
Unanue
E R
ER
Chaplin
D D
DD
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics*; D005347:Fibroblasts; D005786:Gene Expression Regulation; D007118:Immunoassay; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D010957:Plasmids; D011498:Protein Precursors / Q000235:genetics*; D014162:Transfection
D007375:Interleukin-1; D011498:Protein Precursors; C043830:interleukin 1 precursor; D004247:DNA