Biomaterial Database

Tumor necrosis factor and interleukin-1 down-regulate receptors for substance P in human astrocytoma cells. 1991

C L Johnson, and C G Johnson

Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267-0575.

This study examined the influence of cytokines on substance P (SP) receptors (NK1 subtype) in the human astrocytoma cell line UC11. Following trypsinization and passage, the density of SP receptors in these cells was rather low but gradually increased several fold over the course of a few days in culture. Frequent replacement of the growth medium enhanced the density of receptors even more, suggesting that growth factors in the culture medium may determine the levels of receptor. Exposure of the cells to sub-nanomolar concentrations of tumor necrosis factor (TNF alpha) or interleukin-1 beta (IL1 beta), but not interleukin-2 or interleukin-6, decreased the density of SP receptors. This was accompanied by a decrease in the ability of SP to stimulate inositolphosphate formation. The ability of histamine to activate inositolphosphate formation was not influenced by the cytokines. The decrease in SP receptor density was readily reversible on washout of the cytokines. The EC50 for TNF alpha was approximately 0.5 ng/ml, the EC50 for IL1 beta was approximately 0.1 ng/ml. Radioligand binding studies with [125I]TNF alpha indicated the presence of a low density of high affinity binding sites for this ligand: Kd = 2.5 +/- 0.6 ng/ml, Bmax = 14.8 +/- 2.7 fmol bound/mg protein (assuming trimeric form of ligand bound). The most likely explanation for the cytokine effect is an inhibition of the synthesis of new receptors.

UI	MeSH Term	Description	Entries
D007295	Inositol Phosphates	Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.	Inositol Phosphate,Phosphate, Inositol,Phosphates, Inositol
D007375	Interleukin-1	A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.	IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D001932	Brain Neoplasms	Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.	Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D006632	Histamine	An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.	Ceplene,Histamine Dihydrochloride,Histamine Hydrochloride,Peremin
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001254	Astrocytoma	Neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors. Fibrillary astrocytomas are the most common type and may be classified in order of increasing malignancy (grades I through IV). In the first two decades of life, astrocytomas tend to originate in the cerebellar hemispheres; in adults, they most frequently arise in the cerebrum and frequently undergo malignant transformation. (From Devita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2013-7; Holland et al., Cancer Medicine, 3d ed, p1082)	Astrocytoma, Subependymal Giant Cell,Glioma, Astrocytic,Oligoastrocytoma, Mixed,Pleomorphic Xanthoastrocytomas,Anaplastic Astrocytoma,Astrocytoma, Grade I,Astrocytoma, Grade II,Astrocytoma, Grade III,Astrocytoma, Protoplasmic,Astroglioma,Cerebral Astrocytoma,Childhood Cerebral Astrocytoma,Fibrillary Astrocytoma,Gemistocytic Astrocytoma,Intracranial Astrocytoma,Juvenile Pilocytic Astrocytoma,Pilocytic Astrocytoma,Subependymal Giant Cell Astrocytoma,Anaplastic Astrocytomas,Astrocytic Glioma,Astrocytic Gliomas,Astrocytoma, Anaplastic,Astrocytoma, Cerebral,Astrocytoma, Childhood Cerebral,Astrocytoma, Fibrillary,Astrocytoma, Gemistocytic,Astrocytoma, Intracranial,Astrocytoma, Juvenile Pilocytic,Astrocytoma, Pilocytic,Astrocytomas,Astrocytomas, Grade III,Astrogliomas,Cerebral Astrocytoma, Childhood,Cerebral Astrocytomas,Childhood Cerebral Astrocytomas,Fibrillary Astrocytomas,Gemistocytic Astrocytomas,Gliomas, Astrocytic,Grade I Astrocytoma,Grade I Astrocytomas,Grade II Astrocytoma,Grade II Astrocytomas,Grade III Astrocytoma,Grade III Astrocytomas,Intracranial Astrocytomas,Juvenile Pilocytic Astrocytomas,Mixed Oligoastrocytoma,Mixed Oligoastrocytomas,Pilocytic Astrocytoma, Juvenile,Pilocytic Astrocytomas,Pleomorphic Xanthoastrocytoma,Protoplasmic Astrocytoma,Protoplasmic Astrocytomas,Xanthoastrocytoma, Pleomorphic
D013373	Substance P	An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.	Euler-Gaddum Substance P,Hypothalamic Substance P,SP(1-11),Euler Gaddum Substance P,Substance P, Euler-Gaddum,Substance P, Hypothalamic
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D014409	Tumor Necrosis Factor-alpha	Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.	Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha