Mechanisms for the stimulation of prostanoid synthesis by cyclosporine and bacterial lipopolysacch aride

H. Zhang, H. Kaseki, W. B. Davis, R. L. Whisler, D. G. Cornwell

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Both cyclosporine and bacterial lipopolysaccharide enhance prostanoid synthesis and regulate the immune response. This study was designed to establish whether these agents affect prostanoid synthesis by common or different mechanisms. CsA and LPS stimulate prostanoid synthesis both in human monocytes and smooth muscle cells from guinea pig aorta. Only LPS stimulates synthesis in the presence of exogenous arachidonic acid. Dexamethasone totally blocks CsA but only partially inhibits LPS. CsA and LPS both enhance the release of labeled metabolites from cells labeled with arachidonic acid, but indomethacin only blocks the effect of LPS. CsA and the releasing agent calcium ionophore (A23187) both increase PGE2 and PGI2 synthesis without changing their relative concentrations, cause the release of free arachidonic acid, and lead to the formation of new metabolites that are not products of cyclooxygenase activity. Preincubation with either CsA or A23187 and a subsequent wash deplete the arachidonic acid pool available for prostanoid synthesis. Thus, A23187 and CsA have very similar effects on arachidonic acid metabolism. In contrast, LPS increases PGE2 and PGI2 synthesis and alters their relative concentrations, diminishes the relative concentration of free arachidonic acid, and enhances the formation of new metabolites that are products of cyclooxygenase activity. These differences are explained by mechanisms in which CsA promotes prostanoid synthesis through arachidonic acid release, and LPS promotes prostanoid synthesis through increased cyclooxygenase activity.

Original languageEnglish (US)
Pages (from-to)864-871
Number of pages8
JournalTransplantation
Volume47
Issue number5
StatePublished - Jan 1 1989

Fingerprint

Arachidonic Acid
Cyclosporine
Prostaglandins
Calcimycin
Prostaglandin-Endoperoxide Synthases
Epoprostenol
Dinoprostone
Calcium Ionophores
Indomethacin
Dexamethasone
Smooth Muscle Myocytes
Lipopolysaccharides
Aorta
Monocytes
Guinea Pigs

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Mechanisms for the stimulation of prostanoid synthesis by cyclosporine and bacterial lipopolysacch aride. / Zhang, H.; Kaseki, H.; Davis, W. B.; Whisler, R. L.; Cornwell, D. G.

In: Transplantation, Vol. 47, No. 5, 01.01.1989, p. 864-871.

Research output: Contribution to journalArticle

Zhang, H, Kaseki, H, Davis, WB, Whisler, RL & Cornwell, DG 1989, 'Mechanisms for the stimulation of prostanoid synthesis by cyclosporine and bacterial lipopolysacch aride', Transplantation, vol. 47, no. 5, pp. 864-871.
Zhang, H. ; Kaseki, H. ; Davis, W. B. ; Whisler, R. L. ; Cornwell, D. G. / Mechanisms for the stimulation of prostanoid synthesis by cyclosporine and bacterial lipopolysacch aride. In: Transplantation. 1989 ; Vol. 47, No. 5. pp. 864-871.
@article{6f5e588e2f8142edb9c5c06cdc07081c,
title = "Mechanisms for the stimulation of prostanoid synthesis by cyclosporine and bacterial lipopolysacch aride",
abstract = "Both cyclosporine and bacterial lipopolysaccharide enhance prostanoid synthesis and regulate the immune response. This study was designed to establish whether these agents affect prostanoid synthesis by common or different mechanisms. CsA and LPS stimulate prostanoid synthesis both in human monocytes and smooth muscle cells from guinea pig aorta. Only LPS stimulates synthesis in the presence of exogenous arachidonic acid. Dexamethasone totally blocks CsA but only partially inhibits LPS. CsA and LPS both enhance the release of labeled metabolites from cells labeled with arachidonic acid, but indomethacin only blocks the effect of LPS. CsA and the releasing agent calcium ionophore (A23187) both increase PGE2 and PGI2 synthesis without changing their relative concentrations, cause the release of free arachidonic acid, and lead to the formation of new metabolites that are not products of cyclooxygenase activity. Preincubation with either CsA or A23187 and a subsequent wash deplete the arachidonic acid pool available for prostanoid synthesis. Thus, A23187 and CsA have very similar effects on arachidonic acid metabolism. In contrast, LPS increases PGE2 and PGI2 synthesis and alters their relative concentrations, diminishes the relative concentration of free arachidonic acid, and enhances the formation of new metabolites that are products of cyclooxygenase activity. These differences are explained by mechanisms in which CsA promotes prostanoid synthesis through arachidonic acid release, and LPS promotes prostanoid synthesis through increased cyclooxygenase activity.",
author = "H. Zhang and H. Kaseki and Davis, {W. B.} and Whisler, {R. L.} and Cornwell, {D. G.}",
year = "1989",
month = "1",
day = "1",
language = "English (US)",
volume = "47",
pages = "864--871",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Mechanisms for the stimulation of prostanoid synthesis by cyclosporine and bacterial lipopolysacch aride

AU - Zhang, H.

AU - Kaseki, H.

AU - Davis, W. B.

AU - Whisler, R. L.

AU - Cornwell, D. G.

PY - 1989/1/1

Y1 - 1989/1/1

N2 - Both cyclosporine and bacterial lipopolysaccharide enhance prostanoid synthesis and regulate the immune response. This study was designed to establish whether these agents affect prostanoid synthesis by common or different mechanisms. CsA and LPS stimulate prostanoid synthesis both in human monocytes and smooth muscle cells from guinea pig aorta. Only LPS stimulates synthesis in the presence of exogenous arachidonic acid. Dexamethasone totally blocks CsA but only partially inhibits LPS. CsA and LPS both enhance the release of labeled metabolites from cells labeled with arachidonic acid, but indomethacin only blocks the effect of LPS. CsA and the releasing agent calcium ionophore (A23187) both increase PGE2 and PGI2 synthesis without changing their relative concentrations, cause the release of free arachidonic acid, and lead to the formation of new metabolites that are not products of cyclooxygenase activity. Preincubation with either CsA or A23187 and a subsequent wash deplete the arachidonic acid pool available for prostanoid synthesis. Thus, A23187 and CsA have very similar effects on arachidonic acid metabolism. In contrast, LPS increases PGE2 and PGI2 synthesis and alters their relative concentrations, diminishes the relative concentration of free arachidonic acid, and enhances the formation of new metabolites that are products of cyclooxygenase activity. These differences are explained by mechanisms in which CsA promotes prostanoid synthesis through arachidonic acid release, and LPS promotes prostanoid synthesis through increased cyclooxygenase activity.

AB - Both cyclosporine and bacterial lipopolysaccharide enhance prostanoid synthesis and regulate the immune response. This study was designed to establish whether these agents affect prostanoid synthesis by common or different mechanisms. CsA and LPS stimulate prostanoid synthesis both in human monocytes and smooth muscle cells from guinea pig aorta. Only LPS stimulates synthesis in the presence of exogenous arachidonic acid. Dexamethasone totally blocks CsA but only partially inhibits LPS. CsA and LPS both enhance the release of labeled metabolites from cells labeled with arachidonic acid, but indomethacin only blocks the effect of LPS. CsA and the releasing agent calcium ionophore (A23187) both increase PGE2 and PGI2 synthesis without changing their relative concentrations, cause the release of free arachidonic acid, and lead to the formation of new metabolites that are not products of cyclooxygenase activity. Preincubation with either CsA or A23187 and a subsequent wash deplete the arachidonic acid pool available for prostanoid synthesis. Thus, A23187 and CsA have very similar effects on arachidonic acid metabolism. In contrast, LPS increases PGE2 and PGI2 synthesis and alters their relative concentrations, diminishes the relative concentration of free arachidonic acid, and enhances the formation of new metabolites that are products of cyclooxygenase activity. These differences are explained by mechanisms in which CsA promotes prostanoid synthesis through arachidonic acid release, and LPS promotes prostanoid synthesis through increased cyclooxygenase activity.

UR - http://www.scopus.com/inward/record.url?scp=0024411490&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024411490&partnerID=8YFLogxK

M3 - Article

VL - 47

SP - 864

EP - 871

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 5

ER -