Protein kinase A inhibitors reverse histamine-mediated regulation of IL- 5 secretion

Larisa Y Poluektova, Manzoor M. Khan

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Histamine and IL-5 are important autacoid mediators involved in the etiology of allergic diseases. IL-5 is the main factor of eosinophilic reactions in allergy. It has been suggested that the protein kinase A- dependent (PKA) pathway of signal transduction may play the main role in histamine-induced elevation of interleukin-5 production. This study was designed to investigate the effects of the inhibitors of regulatory and catalytic subunits of PKA on histamine-mediated elevation of IL-5 production. In our study, histamine at a concentration range of 10-4-10-6 M enhanced IL-5 production in D10.G4.1 cells, a mouse Th2 helper cell line. Pretreatment of this cell line with histamine at a concentration of 10-4 M for 6-9 h had the maximum stimulatory effects (226-420%) on IL-5 production. Other cAMP-elevating agents including forskolin and Bt2-cAMP produced similar effects. The PKA inhibitors N-[2-(methylaminoethyl]-5-isoquinoline- sulfonamide (H-8) and Rp-diastereomer of adenosine cyclic 3',5'- phosphorothioate (Rp-cAMPS) were used for the inhibition of catalytic and regulatory subunits of PKA, respectively. Pretreatment of D10.G4.1 cells with H-8 at a concentration of 10-5 M completely prevented the effects of histamine at a concentration range of 10-6-10-4 M. Rp-cAMPS at 10-5 M also prevented histamine-induced stimulation. Neither inhibitor affected IL- 5 production when tested alone. These observations suggest a role for PKA in histamine-mediated increase in IL-5 production.

Original languageEnglish (US)
Pages (from-to)9-19
Number of pages11
JournalImmunopharmacology
Volume39
Issue number1
DOIs
StatePublished - Mar 1 1998

Fingerprint

Interleukin-5
Protein Kinase Inhibitors
Cyclic AMP-Dependent Protein Kinases
Histamine
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
Autacoids
Cell Line
Th2 Cells
Colforsin
Helper-Inducer T-Lymphocytes
Signal Transduction
Catalytic Domain
Hypersensitivity

Keywords

  • D10.G4.1 mouse Th2 helper cells
  • H-8
  • Histamine
  • Interleukin-5
  • Protein kinase A
  • Rp-cAMPS

ASJC Scopus subject areas

  • Pharmacology

Cite this

Protein kinase A inhibitors reverse histamine-mediated regulation of IL- 5 secretion. / Poluektova, Larisa Y; Khan, Manzoor M.

In: Immunopharmacology, Vol. 39, No. 1, 01.03.1998, p. 9-19.

Research output: Contribution to journalArticle

@article{8f5fc48b64324eb38cf3f10fddd6a909,
title = "Protein kinase A inhibitors reverse histamine-mediated regulation of IL- 5 secretion",
abstract = "Histamine and IL-5 are important autacoid mediators involved in the etiology of allergic diseases. IL-5 is the main factor of eosinophilic reactions in allergy. It has been suggested that the protein kinase A- dependent (PKA) pathway of signal transduction may play the main role in histamine-induced elevation of interleukin-5 production. This study was designed to investigate the effects of the inhibitors of regulatory and catalytic subunits of PKA on histamine-mediated elevation of IL-5 production. In our study, histamine at a concentration range of 10-4-10-6 M enhanced IL-5 production in D10.G4.1 cells, a mouse Th2 helper cell line. Pretreatment of this cell line with histamine at a concentration of 10-4 M for 6-9 h had the maximum stimulatory effects (226-420{\%}) on IL-5 production. Other cAMP-elevating agents including forskolin and Bt2-cAMP produced similar effects. The PKA inhibitors N-[2-(methylaminoethyl]-5-isoquinoline- sulfonamide (H-8) and Rp-diastereomer of adenosine cyclic 3',5'- phosphorothioate (Rp-cAMPS) were used for the inhibition of catalytic and regulatory subunits of PKA, respectively. Pretreatment of D10.G4.1 cells with H-8 at a concentration of 10-5 M completely prevented the effects of histamine at a concentration range of 10-6-10-4 M. Rp-cAMPS at 10-5 M also prevented histamine-induced stimulation. Neither inhibitor affected IL- 5 production when tested alone. These observations suggest a role for PKA in histamine-mediated increase in IL-5 production.",
keywords = "D10.G4.1 mouse Th2 helper cells, H-8, Histamine, Interleukin-5, Protein kinase A, Rp-cAMPS",
author = "Poluektova, {Larisa Y} and Khan, {Manzoor M.}",
year = "1998",
month = "3",
day = "1",
doi = "10.1016/S0162-3109(97)00093-3",
language = "English (US)",
volume = "39",
pages = "9--19",
journal = "Immunopharmacology",
issn = "0162-3109",
publisher = "Elsevier BV",
number = "1",

}

TY - JOUR

T1 - Protein kinase A inhibitors reverse histamine-mediated regulation of IL- 5 secretion

AU - Poluektova, Larisa Y

AU - Khan, Manzoor M.

PY - 1998/3/1

Y1 - 1998/3/1

N2 - Histamine and IL-5 are important autacoid mediators involved in the etiology of allergic diseases. IL-5 is the main factor of eosinophilic reactions in allergy. It has been suggested that the protein kinase A- dependent (PKA) pathway of signal transduction may play the main role in histamine-induced elevation of interleukin-5 production. This study was designed to investigate the effects of the inhibitors of regulatory and catalytic subunits of PKA on histamine-mediated elevation of IL-5 production. In our study, histamine at a concentration range of 10-4-10-6 M enhanced IL-5 production in D10.G4.1 cells, a mouse Th2 helper cell line. Pretreatment of this cell line with histamine at a concentration of 10-4 M for 6-9 h had the maximum stimulatory effects (226-420%) on IL-5 production. Other cAMP-elevating agents including forskolin and Bt2-cAMP produced similar effects. The PKA inhibitors N-[2-(methylaminoethyl]-5-isoquinoline- sulfonamide (H-8) and Rp-diastereomer of adenosine cyclic 3',5'- phosphorothioate (Rp-cAMPS) were used for the inhibition of catalytic and regulatory subunits of PKA, respectively. Pretreatment of D10.G4.1 cells with H-8 at a concentration of 10-5 M completely prevented the effects of histamine at a concentration range of 10-6-10-4 M. Rp-cAMPS at 10-5 M also prevented histamine-induced stimulation. Neither inhibitor affected IL- 5 production when tested alone. These observations suggest a role for PKA in histamine-mediated increase in IL-5 production.

AB - Histamine and IL-5 are important autacoid mediators involved in the etiology of allergic diseases. IL-5 is the main factor of eosinophilic reactions in allergy. It has been suggested that the protein kinase A- dependent (PKA) pathway of signal transduction may play the main role in histamine-induced elevation of interleukin-5 production. This study was designed to investigate the effects of the inhibitors of regulatory and catalytic subunits of PKA on histamine-mediated elevation of IL-5 production. In our study, histamine at a concentration range of 10-4-10-6 M enhanced IL-5 production in D10.G4.1 cells, a mouse Th2 helper cell line. Pretreatment of this cell line with histamine at a concentration of 10-4 M for 6-9 h had the maximum stimulatory effects (226-420%) on IL-5 production. Other cAMP-elevating agents including forskolin and Bt2-cAMP produced similar effects. The PKA inhibitors N-[2-(methylaminoethyl]-5-isoquinoline- sulfonamide (H-8) and Rp-diastereomer of adenosine cyclic 3',5'- phosphorothioate (Rp-cAMPS) were used for the inhibition of catalytic and regulatory subunits of PKA, respectively. Pretreatment of D10.G4.1 cells with H-8 at a concentration of 10-5 M completely prevented the effects of histamine at a concentration range of 10-6-10-4 M. Rp-cAMPS at 10-5 M also prevented histamine-induced stimulation. Neither inhibitor affected IL- 5 production when tested alone. These observations suggest a role for PKA in histamine-mediated increase in IL-5 production.

KW - D10.G4.1 mouse Th2 helper cells

KW - H-8

KW - Histamine

KW - Interleukin-5

KW - Protein kinase A

KW - Rp-cAMPS

UR - http://www.scopus.com/inward/record.url?scp=0031810595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031810595&partnerID=8YFLogxK

U2 - 10.1016/S0162-3109(97)00093-3

DO - 10.1016/S0162-3109(97)00093-3

M3 - Article

VL - 39

SP - 9

EP - 19

JO - Immunopharmacology

JF - Immunopharmacology

SN - 0162-3109

IS - 1

ER -