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.

[1]  H. Colten,et al.  Macrophage membrane interleukin 1 regulates the expression of acute phase proteins in human hepatoma Hep 3B cells. , 1987, Journal of immunology.

[2]  T. Hopp,et al.  Localization of human mononuclear cell interleukin 1. , 1987, Journal of immunology.

[3]  E. Unanue,et al.  Regulation of interleukin 1 gene expression by adherence and lipopolysaccharide. , 1987, Journal of immunology.

[4]  K. Prickett,et al.  The interleukin-1 receptor binds the human interleukin-1 alpha precursor but not the interleukin-1 beta precursor. , 1987, The Journal of biological chemistry.

[5]  M. Melli,et al.  The murine interleukin 1β gene: structure and evolution , 1986 .

[6]  D. Goeddel,et al.  Two interleukin 1 genes in the mouse: cloning and expression of the cDNA for murine interleukin 1 beta. , 1986, Journal of immunology.

[7]  T. Hopp,et al.  The cell surface receptors for interleukin-1α and interleukin-1β are identical , 1986, Nature.

[8]  A. C. Webb,et al.  Genomic sequence for human prointerleukin 1 beta: possible evolution from a reverse transcribed prointerleukin 1 alpha gene. , 1986, Nucleic acids research.

[9]  H. Young,et al.  Intracellular localization of human monocyte associated interleukin 1 (IL 1) activity and release of biologically active IL 1 from monocytes by trypsin and plasmin. , 1986, Journal of immunology.

[10]  M. Yamada,et al.  Complete nucleotide sequence of the gene for human interleukin 1 alpha. , 1986, Nucleic acids research.

[11]  C. Dinarello.  Interleukin-1: amino acid sequences, multiple biological activities and comparison with tumor necrosis factor (cachectin). , 1986, The Year in immunology.

[12]  J. Seidman,et al.  Expression of murine 21-hydroxylase in mouse adrenal glands and in transfected Y1 adrenocortical tumor cells. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[13]  T. Mak,et al.  Reconstitution of an active surface T3/T-cell antigen receptor by DNA transfer , 1985, Nature.

[14]  C. March,et al.  Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs , 1985, Nature.

[15]  E. Unanue,et al.  Identification of a membrane-associated interleukin 1 in macrophages. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[16]  R. Axel,et al.  The isolation and sequence of the gene encoding T8: A molecule defining functional classes of T lymphocytes , 1985, Cell.

[17]  S. Durum,et al.  Interleukin 1: an immunological perspective. , 1985, Annual review of immunology.

[18]  A. C. Webb,et al.  Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[19]  C. Janeway,et al.  Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: interleukin 1 is required for the expression of receptors for interleukin 2. , 1984, Journal of immunology.

[20]  R. Kampschmidt,et al.  The Numerous Postulated Biological Manifestations of Interleukin‐1 , 1984, Journal of leukocyte biology.

[21]  C. Janeway,et al.  Induction of receptors for interleukin 2 requires T cell Ag:Ia receptor crosslinking and interleukin 1. , 1984, Lymphokine research.

[22]  P. Lomedico,et al.  Cloning and expression of murine interleukin-1 cDNA in Escherichia coli , 1984, Nature.

[23]  P Berg,et al.  Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. , 1982, Journal of molecular and applied genetics.

[24]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.