Biomaterial Database

Inhibition of interleukin-2 production by tumor cell products and by CKS-17, a synthetic retroviral envelope peptide. 1990

M Nelson, and D Nelson

Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia.

Tumor cells of all types and species tested have been found to produce, in culture, substances that depress the expression of cell-mediated immunity, in the form of delayed-type hypersensitivity reactions in mouse feet. The factors responsible appear related immunologically to the retroviral envelope protein p15E. We have measured the effects of tumor products and conjugates of a p15E-related peptide, CKS-17, on interleukin-2 (IL-2) production by cultured, mitogen-stimulated EL4 cells; in this system IL-2 production is independent of IL-1. Supernatants of cultures of mouse, human and guinea-pig tumor cells inhibited IL-2 production in a dose-dependent fashion. CKS-17 conjugates, but not control conjugates, also inhibited IL-2 production. Responses to IL-2 of the CTLL line used were less inhibited by tumor products and very slightly inhibited by CKS-17 conjugates. IL-2 receptor density, assayed by flow cytometry, was not inhibited. IL-2 production was inhibited whether the tumor products or CKS-17 conjugates were added early or late in the course of culture of stimulated EL4 cells. Inhibition by CKS-17 conjugates was selective in that IL-2 production was inhibited to a greater degree than general protein synthesis in EL4 cells, and general protein synthesis by fibroblasts was unaffected. Measurement of IL-2 mRNA suggested that inhibition of IL-2 production was mediated post-transcriptionally. Fractionation of six different tumor supernatants on Sephacryl S-300 revealed a single peak of activity with an apparent molecular mass of 18 kDa. Antibodies to CKS-17 conjugates neutralized the inhibitory effect of native tumor products on IL-2 production. Inhibition of IL-2 production, by factors related to p15E, provides a strategically effective means of subversion of host defenses by tumors, and abrogation of this inhibition by means of antibodies might promote host resistance to tumor growth.

UI	MeSH Term	Description	Entries
D007376	Interleukin-2	A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.	IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D008808	Mice, Inbred CBA	An inbred strain of mouse that is widely used in BIOMEDICAL RESEARCH.	Mice, CBA,Mouse, CBA,Mouse, Inbred CBA,CBA Mice,CBA Mice, Inbred,CBA Mouse,CBA Mouse, Inbred,Inbred CBA Mice,Inbred CBA Mouse
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009363	Neoplasm Proteins	Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.	Proteins, Neoplasm
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D003208	Concanavalin A	A MANNOSE/GLUCOSE binding lectin isolated from the jack bean (Canavalia ensiformis). It is a potent mitogen used to stimulate cell proliferation in lymphocytes, primarily T-lymphocyte, cultures.
D003513	Cycloheximide	Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.	Actidione,Cicloheximide
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia