Ca2+ responses to interleukin 1 and tumor necrosis factor in cultured human skin fibroblasts: Possible implications for reye syndrome

Barbara E. Corkey, Jean François Geschwind, Jude T. Deeney, Daniel E. Hale, Steven D. Douglas, Laurie Kilpatrick

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Elevated concentrations of cytokines were found in the plasma of patients acutely ill with Reye syndrome (RS) but not in control subjects or recovered RS patients. To determine whether this disorder involves a genetically determined abnormal response to cytokines, the effects of tumor necrosis factor (TNF) and IL-1 on intracellular free Ca2+ were compared in cultured skin fibroblasts from control subjects and patients with RS. IL-1 and TNF caused rapid, transient, and concentration-dependent increases in cytosolic free Ca2+. The peak cytosolic free Ca2+ was greater and occurred at higher concentrations of IL-1 and TNF in patient cells than in cells from age-matched controls. In control cells, the Ca2+ transient diminished sharply with increasing amounts of IL-1 or TNF above the maximum stimulatory concentration. In contrast, in patient fibroblasts this bell-shaped curve of concentration dependency was much less apparent. Brady kinin-stimulated Ca2+ transients were similar in the two groups and did not exhibit the bell-shaped concentration dependency. Thus, plasma cytokine levels are elevated in RS patients and the Ca2+ response to cytokines is increased in cells derived from these patients. We propose that the increased response reflects a genetic defect in cytokine receptor-modulated signal transduction.

Original languageEnglish (US)
Pages (from-to)778-786
Number of pages9
JournalJournal of Clinical Investigation
Volume87
Issue number3
DOIs
StatePublished - Jan 1 1991

Fingerprint

Reye Syndrome
Interleukin-1
Tumor Necrosis Factor-alpha
Fibroblasts
Skin
Cytokines
Kinins
Cytokine Receptors
Signal Transduction

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Corkey, Barbara E. ; Geschwind, Jean François ; Deeney, Jude T. ; Hale, Daniel E. ; Douglas, Steven D. ; Kilpatrick, Laurie. / Ca2+ responses to interleukin 1 and tumor necrosis factor in cultured human skin fibroblasts : Possible implications for reye syndrome. In: Journal of Clinical Investigation. 1991 ; Vol. 87, No. 3. pp. 778-786.
@article{cb200e6db2324d518eb54ad4c65f6f99,
title = "Ca2+ responses to interleukin 1 and tumor necrosis factor in cultured human skin fibroblasts: Possible implications for reye syndrome",
abstract = "Elevated concentrations of cytokines were found in the plasma of patients acutely ill with Reye syndrome (RS) but not in control subjects or recovered RS patients. To determine whether this disorder involves a genetically determined abnormal response to cytokines, the effects of tumor necrosis factor (TNF) and IL-1 on intracellular free Ca2+ were compared in cultured skin fibroblasts from control subjects and patients with RS. IL-1 and TNF caused rapid, transient, and concentration-dependent increases in cytosolic free Ca2+. The peak cytosolic free Ca2+ was greater and occurred at higher concentrations of IL-1 and TNF in patient cells than in cells from age-matched controls. In control cells, the Ca2+ transient diminished sharply with increasing amounts of IL-1 or TNF above the maximum stimulatory concentration. In contrast, in patient fibroblasts this bell-shaped curve of concentration dependency was much less apparent. Brady kinin-stimulated Ca2+ transients were similar in the two groups and did not exhibit the bell-shaped concentration dependency. Thus, plasma cytokine levels are elevated in RS patients and the Ca2+ response to cytokines is increased in cells derived from these patients. We propose that the increased response reflects a genetic defect in cytokine receptor-modulated signal transduction.",
author = "Corkey, {Barbara E.} and Geschwind, {Jean Fran{\cc}ois} and Deeney, {Jude T.} and Hale, {Daniel E.} and Douglas, {Steven D.} and Laurie Kilpatrick",
year = "1991",
month = "1",
day = "1",
doi = "10.1172/JCI115081",
language = "English (US)",
volume = "87",
pages = "778--786",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "3",

}

Ca2+ responses to interleukin 1 and tumor necrosis factor in cultured human skin fibroblasts : Possible implications for reye syndrome. / Corkey, Barbara E.; Geschwind, Jean François; Deeney, Jude T.; Hale, Daniel E.; Douglas, Steven D.; Kilpatrick, Laurie.

In: Journal of Clinical Investigation, Vol. 87, No. 3, 01.01.1991, p. 778-786.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ca2+ responses to interleukin 1 and tumor necrosis factor in cultured human skin fibroblasts

T2 - Possible implications for reye syndrome

AU - Corkey, Barbara E.

AU - Geschwind, Jean François

AU - Deeney, Jude T.

AU - Hale, Daniel E.

AU - Douglas, Steven D.

AU - Kilpatrick, Laurie

PY - 1991/1/1

Y1 - 1991/1/1

N2 - Elevated concentrations of cytokines were found in the plasma of patients acutely ill with Reye syndrome (RS) but not in control subjects or recovered RS patients. To determine whether this disorder involves a genetically determined abnormal response to cytokines, the effects of tumor necrosis factor (TNF) and IL-1 on intracellular free Ca2+ were compared in cultured skin fibroblasts from control subjects and patients with RS. IL-1 and TNF caused rapid, transient, and concentration-dependent increases in cytosolic free Ca2+. The peak cytosolic free Ca2+ was greater and occurred at higher concentrations of IL-1 and TNF in patient cells than in cells from age-matched controls. In control cells, the Ca2+ transient diminished sharply with increasing amounts of IL-1 or TNF above the maximum stimulatory concentration. In contrast, in patient fibroblasts this bell-shaped curve of concentration dependency was much less apparent. Brady kinin-stimulated Ca2+ transients were similar in the two groups and did not exhibit the bell-shaped concentration dependency. Thus, plasma cytokine levels are elevated in RS patients and the Ca2+ response to cytokines is increased in cells derived from these patients. We propose that the increased response reflects a genetic defect in cytokine receptor-modulated signal transduction.

AB - Elevated concentrations of cytokines were found in the plasma of patients acutely ill with Reye syndrome (RS) but not in control subjects or recovered RS patients. To determine whether this disorder involves a genetically determined abnormal response to cytokines, the effects of tumor necrosis factor (TNF) and IL-1 on intracellular free Ca2+ were compared in cultured skin fibroblasts from control subjects and patients with RS. IL-1 and TNF caused rapid, transient, and concentration-dependent increases in cytosolic free Ca2+. The peak cytosolic free Ca2+ was greater and occurred at higher concentrations of IL-1 and TNF in patient cells than in cells from age-matched controls. In control cells, the Ca2+ transient diminished sharply with increasing amounts of IL-1 or TNF above the maximum stimulatory concentration. In contrast, in patient fibroblasts this bell-shaped curve of concentration dependency was much less apparent. Brady kinin-stimulated Ca2+ transients were similar in the two groups and did not exhibit the bell-shaped concentration dependency. Thus, plasma cytokine levels are elevated in RS patients and the Ca2+ response to cytokines is increased in cells derived from these patients. We propose that the increased response reflects a genetic defect in cytokine receptor-modulated signal transduction.

UR - http://www.scopus.com/inward/record.url?scp=0025922517&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025922517&partnerID=8YFLogxK

U2 - 10.1172/JCI115081

DO - 10.1172/JCI115081

M3 - Article

C2 - 1847937

AN - SCOPUS:0025922517

VL - 87

SP - 778

EP - 786

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 3

ER -