Prostanoids mediate IL-1β-induced β-adrenergic hyporesponsiveness in human airway smooth muscle cells

Johanne D. Laporte, Paul E. Moore, Reynold Panettieri, Winfried Moeller, Joachim Heyder, Stephanie A. Shore

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

We have previously reported that pretreatment of cultured human airway smooth muscle (HASM) cells with interleukin-1β (IL-1β) results in decreased β-adrenergic responsiveness. The purpose of this study was to determine whether prostanoids released as a result of cyclooxygenase-2 (COX-2) induction by IL-1β contribute to this effect of the cytokine. Confluent serum-deprived HASM cells were studied in passages 4-7. IL-1β (20 ng/ml for 22 h) reduced the ability of the β-agonist isoproterenol (Iso) to decrease stiffness of HASM cells as measured by magnetic twisting cytometry. The effect of IL-1β on Iso-induced changes in cell stiffness was abolished by nonselective [indomethacin (Indo), 10-6 M] and selective (NS-398, 10-5 M) COX-2 inhibitors. Indo and NS-398 also inhibited both the increased basal cAMP and the decreases in Iso-stimulated cAMP production induced by IL-1β. IL-1β (20 ng/ml for 22 h) caused an increase in both basal (15-fold) and arachidonic acid (AA)-stimulated (10-fold) PGE2 release. Indo blocked basal and AA-stimulated PGE2 release in both control and IL-1β-treated cells. NS- 398 also markedly reduced basal and AA-stimulated PGE2 release in IL-1β- treated cells but had no significant effect on AA-stimulated PGE2 release in control cells. Western blot analysis confirmed the induction of COX-2 by IL- 1β. Exogenously administered PGE2 (10-7 M, 22 h) caused a significant reduction in the ability of Iso to decrease cell stiffness, mimicking the effects of IL-1β. Cycloheximide (10 μg/ml for 24 h), an inhibitor of protein synthesis, also abolished the effects of IL-1β on Iso-induced cell stiffness changes and cAMP formation. In summary, our results indicate that IL-1β significantly increases prostanoid release by HASM cells as a result of increased COX-2 expression. The prostanoids appear to contribute to β- adrenergic hyporesponsiveness, perhaps by heterologous desensitization of the β2 receptor.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume275
Issue number3 19-3
StatePublished - Sep 1 1998

Fingerprint

Interleukin-1
Adrenergic Agents
Prostaglandins
Smooth Muscle Myocytes
Isoproterenol
Dinoprostone
Arachidonic Acid
Cyclooxygenase 2
Indomethacin
Protein Synthesis Inhibitors
Cyclooxygenase 2 Inhibitors
Cycloheximide
Western Blotting
Cytokines

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Keywords

  • Adenosine 3',5'-cyclic monophosphate
  • Cytoskeletal mechanics
  • Indomethacin
  • Interleukin-1β
  • NS-398
  • Prostaglandin E

Cite this

Laporte, Johanne D. ; Moore, Paul E. ; Panettieri, Reynold ; Moeller, Winfried ; Heyder, Joachim ; Shore, Stephanie A. / Prostanoids mediate IL-1β-induced β-adrenergic hyporesponsiveness in human airway smooth muscle cells. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 1998 ; Vol. 275, No. 3 19-3.
@article{77d007f4aa7e4245b8b54288f130906f,
title = "Prostanoids mediate IL-1β-induced β-adrenergic hyporesponsiveness in human airway smooth muscle cells",
abstract = "We have previously reported that pretreatment of cultured human airway smooth muscle (HASM) cells with interleukin-1β (IL-1β) results in decreased β-adrenergic responsiveness. The purpose of this study was to determine whether prostanoids released as a result of cyclooxygenase-2 (COX-2) induction by IL-1β contribute to this effect of the cytokine. Confluent serum-deprived HASM cells were studied in passages 4-7. IL-1β (20 ng/ml for 22 h) reduced the ability of the β-agonist isoproterenol (Iso) to decrease stiffness of HASM cells as measured by magnetic twisting cytometry. The effect of IL-1β on Iso-induced changes in cell stiffness was abolished by nonselective [indomethacin (Indo), 10-6 M] and selective (NS-398, 10-5 M) COX-2 inhibitors. Indo and NS-398 also inhibited both the increased basal cAMP and the decreases in Iso-stimulated cAMP production induced by IL-1β. IL-1β (20 ng/ml for 22 h) caused an increase in both basal (15-fold) and arachidonic acid (AA)-stimulated (10-fold) PGE2 release. Indo blocked basal and AA-stimulated PGE2 release in both control and IL-1β-treated cells. NS- 398 also markedly reduced basal and AA-stimulated PGE2 release in IL-1β- treated cells but had no significant effect on AA-stimulated PGE2 release in control cells. Western blot analysis confirmed the induction of COX-2 by IL- 1β. Exogenously administered PGE2 (10-7 M, 22 h) caused a significant reduction in the ability of Iso to decrease cell stiffness, mimicking the effects of IL-1β. Cycloheximide (10 μg/ml for 24 h), an inhibitor of protein synthesis, also abolished the effects of IL-1β on Iso-induced cell stiffness changes and cAMP formation. In summary, our results indicate that IL-1β significantly increases prostanoid release by HASM cells as a result of increased COX-2 expression. The prostanoids appear to contribute to β- adrenergic hyporesponsiveness, perhaps by heterologous desensitization of the β2 receptor.",
keywords = "Adenosine 3',5'-cyclic monophosphate, Cytoskeletal mechanics, Indomethacin, Interleukin-1β, NS-398, Prostaglandin E",
author = "Laporte, {Johanne D.} and Moore, {Paul E.} and Reynold Panettieri and Winfried Moeller and Joachim Heyder and Shore, {Stephanie A.}",
year = "1998",
month = "9",
day = "1",
language = "English (US)",
volume = "275",
journal = "American Journal of Physiology",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "3 19-3",

}

Prostanoids mediate IL-1β-induced β-adrenergic hyporesponsiveness in human airway smooth muscle cells. / Laporte, Johanne D.; Moore, Paul E.; Panettieri, Reynold; Moeller, Winfried; Heyder, Joachim; Shore, Stephanie A.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 275, No. 3 19-3, 01.09.1998.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prostanoids mediate IL-1β-induced β-adrenergic hyporesponsiveness in human airway smooth muscle cells

AU - Laporte, Johanne D.

AU - Moore, Paul E.

AU - Panettieri, Reynold

AU - Moeller, Winfried

AU - Heyder, Joachim

AU - Shore, Stephanie A.

PY - 1998/9/1

Y1 - 1998/9/1

N2 - We have previously reported that pretreatment of cultured human airway smooth muscle (HASM) cells with interleukin-1β (IL-1β) results in decreased β-adrenergic responsiveness. The purpose of this study was to determine whether prostanoids released as a result of cyclooxygenase-2 (COX-2) induction by IL-1β contribute to this effect of the cytokine. Confluent serum-deprived HASM cells were studied in passages 4-7. IL-1β (20 ng/ml for 22 h) reduced the ability of the β-agonist isoproterenol (Iso) to decrease stiffness of HASM cells as measured by magnetic twisting cytometry. The effect of IL-1β on Iso-induced changes in cell stiffness was abolished by nonselective [indomethacin (Indo), 10-6 M] and selective (NS-398, 10-5 M) COX-2 inhibitors. Indo and NS-398 also inhibited both the increased basal cAMP and the decreases in Iso-stimulated cAMP production induced by IL-1β. IL-1β (20 ng/ml for 22 h) caused an increase in both basal (15-fold) and arachidonic acid (AA)-stimulated (10-fold) PGE2 release. Indo blocked basal and AA-stimulated PGE2 release in both control and IL-1β-treated cells. NS- 398 also markedly reduced basal and AA-stimulated PGE2 release in IL-1β- treated cells but had no significant effect on AA-stimulated PGE2 release in control cells. Western blot analysis confirmed the induction of COX-2 by IL- 1β. Exogenously administered PGE2 (10-7 M, 22 h) caused a significant reduction in the ability of Iso to decrease cell stiffness, mimicking the effects of IL-1β. Cycloheximide (10 μg/ml for 24 h), an inhibitor of protein synthesis, also abolished the effects of IL-1β on Iso-induced cell stiffness changes and cAMP formation. In summary, our results indicate that IL-1β significantly increases prostanoid release by HASM cells as a result of increased COX-2 expression. The prostanoids appear to contribute to β- adrenergic hyporesponsiveness, perhaps by heterologous desensitization of the β2 receptor.

AB - We have previously reported that pretreatment of cultured human airway smooth muscle (HASM) cells with interleukin-1β (IL-1β) results in decreased β-adrenergic responsiveness. The purpose of this study was to determine whether prostanoids released as a result of cyclooxygenase-2 (COX-2) induction by IL-1β contribute to this effect of the cytokine. Confluent serum-deprived HASM cells were studied in passages 4-7. IL-1β (20 ng/ml for 22 h) reduced the ability of the β-agonist isoproterenol (Iso) to decrease stiffness of HASM cells as measured by magnetic twisting cytometry. The effect of IL-1β on Iso-induced changes in cell stiffness was abolished by nonselective [indomethacin (Indo), 10-6 M] and selective (NS-398, 10-5 M) COX-2 inhibitors. Indo and NS-398 also inhibited both the increased basal cAMP and the decreases in Iso-stimulated cAMP production induced by IL-1β. IL-1β (20 ng/ml for 22 h) caused an increase in both basal (15-fold) and arachidonic acid (AA)-stimulated (10-fold) PGE2 release. Indo blocked basal and AA-stimulated PGE2 release in both control and IL-1β-treated cells. NS- 398 also markedly reduced basal and AA-stimulated PGE2 release in IL-1β- treated cells but had no significant effect on AA-stimulated PGE2 release in control cells. Western blot analysis confirmed the induction of COX-2 by IL- 1β. Exogenously administered PGE2 (10-7 M, 22 h) caused a significant reduction in the ability of Iso to decrease cell stiffness, mimicking the effects of IL-1β. Cycloheximide (10 μg/ml for 24 h), an inhibitor of protein synthesis, also abolished the effects of IL-1β on Iso-induced cell stiffness changes and cAMP formation. In summary, our results indicate that IL-1β significantly increases prostanoid release by HASM cells as a result of increased COX-2 expression. The prostanoids appear to contribute to β- adrenergic hyporesponsiveness, perhaps by heterologous desensitization of the β2 receptor.

KW - Adenosine 3',5'-cyclic monophosphate

KW - Cytoskeletal mechanics

KW - Indomethacin

KW - Interleukin-1β

KW - NS-398

KW - Prostaglandin E

UR - http://www.scopus.com/inward/record.url?scp=0031658992&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031658992&partnerID=8YFLogxK

M3 - Article

VL - 275

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 1040-0605

IS - 3 19-3

ER -