Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
1991-5-24
|
| pubmed:abstractText |
The cytokine interleukin-1 (IL-1) has a variety of effects in the kidney involving induction of nephritis and renal injury. In addition, recent reports suggest that IL-1 regulates natriuresis and renin secretion in the kidney. To examine the potential sites of action of IL-1 in the kidney, we used iodine-125-labeled recombinant human interleukin-1 alpha ([125I]IL-1 alpha) to identify and characterize IL-1 receptors in crude membrane preparations of mouse (C57BL/6) kidney. The binding of [125I] IL-1 alpha was linear over a broad range of membrane protein concentrations, saturable, reversible, and of high affinity, with an equilibrium dissociation constant (Kd) of 66 +/- 10 pM and a maximum number of binding sites of 1.04 +/- 0.24 fmol/mg protein. In competition studies, recombinant human IL-1 alpha, recombinant human IL-1 beta, and a weak IL-1 beta analog (IL-1 beta+) inhibited [125I]IL-1 alpha binding to mouse kidney in parallel with their relative bioactivities in the T-cell comitogenesis assay, with inhibitory binding affinity constant (Ki) values of 28 +/- 19, 53 +/- 23, and 5560 +/- 2098 pM, respectively; rat/human CRF and human tumor necrosis factor had no effect on [125I]IL-1 alpha binding. In autoradiographic studies, IL-1 receptors were heterogeneously distributed in the kidney, with significantly higher densities present in the medulla than in the cortex. To study the effects of endogenous IL-1 in modulating [125I]IL-1 alpha-binding sites in kidney, we injected 30 micrograms of the bacterial endotoxin lipopolysaccharide (LPS) to mice ip. Autoradiographic studies demonstrated substantial decreases in [125I]IL-1 alpha binding in both the kidney cortex (control, 34.7 +/- 6.2 fmol/mg tissue equivalent; LPS, 11.3 +/- 0.3; P less than 0.05) and medulla (52.7 +/- 8.1 vs. 26.0 +/- 1.0; P less than 0.05) 24 h after injection of LPS. Saturation studies in whole kidney homogenates demonstrated that the LPS-induced decrease in [125I]IL-1 alpha binding was primarily due to a down-regulation of IL-1 receptors (i.e. decrease in the maximum number of binding sites). The identification of IL-1 receptors in kidney with characteristics similar to those of IL-1 receptors in the brain-endocrine-immune axis provides further support for a physiological role for IL-1 in regulating renal function.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0013-7227
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
128
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2618-24
|
| pubmed:dateRevised |
2003-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:1826879-Animals,
pubmed-meshheading:1826879-Autoradiography,
pubmed-meshheading:1826879-Binding Sites,
pubmed-meshheading:1826879-Injections,
pubmed-meshheading:1826879-Interleukin-1,
pubmed-meshheading:1826879-Kidney,
pubmed-meshheading:1826879-Lipopolysaccharides,
pubmed-meshheading:1826879-Mice,
pubmed-meshheading:1826879-Mice, Inbred C57BL,
pubmed-meshheading:1826879-Receptors, Immunologic,
pubmed-meshheading:1826879-Receptors, Interleukin-1,
pubmed-meshheading:1826879-Tissue Distribution
|
| pubmed:year |
1991
|
| pubmed:articleTitle |
Interleukin-1 receptors in mouse kidney: identification, localization, and modulation by lipopolysaccharide treatment.
|
| pubmed:affiliation |
Neurobiology Laboratory, National Institute on Drug Abuse, Baltimore, Maryland 21224.
|
| pubmed:publicationType |
Journal Article
|