Regulation of IL-13 production by histamine in cloned murine T helper type 2 cells

Kathleen A. Elliott; Natalia A. Osna; Margaret A. Scofield; Manzoor M. Khan

doi:10.1016/S1567-5769(01)00117-5

Regulation of IL-13 production by histamine in cloned murine T helper type 2 cells

Kathleen A. Elliott, Natalia A. Osna, Margaret A. Scofield, Manzoor M. Khan

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

Histamine affects the balance of T helper type 1 (Th1) and T helper type 2 (Th2) cytokines by shifting cytokine production from a Th1 to a Th2 pattern. Interleukin-13 (IL-13) is an important autacoid mediator that has been implicated in the development of allergic disease. This study was designed to investigate the mechanisms of regulation of IL-13 by histamine in Th2 cells. D10.G4.1 cells, a murine Th2 cell line, were treated with histamine (10^-8-10^-4 M) and then activated with PMA (phorbol 12 myristate 13-acetate) plus ionomycin or αCD3. Levels of IL-13 production were then measured by enzyme-linked immunosorbent assay (ELISA) and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Cells were pretreated with histamine receptor antagonists pyrilamine, ranitidine, cimetidine and thioperamide to determine the involvement of histamine receptors. Cells were also pretreated with protein kinase A (PKA) inhibitors N-[2-(methylaminoethyl)]-5-isoquinoline-sulfonamide (H-8) and Rp-diastereomer of adenosine cyclic 3′5′-phosphorothionate (Rp-cAMPS), and Janus kinase-signal transducer and activator of transcription (Jak-STAT) inhibitor tyrphostin AG490 prior to the addition of histamine. H-8 is an inhibitor of the catalytic subunit of PKA while Rp-cAMPS is an inhibitor of the regulatory subunit of PKA. Tyrphostin is an inhibitor of Jak2, Jak3, STAT1, STAT3 and STAT5. Finally, cells were pretreated with IL-12, a monokine known to repress STAT6 DNA binding. We found that histamine dose-dependently enhanced IL-13 secretion and mRNA levels in Th2 cells via H1 and H2 receptors. Pretreatment of cells with H-8, Rp-cAMPS and tyrphostin prevented histamine-induced secretion and transcription of IL-13. Likewise, pretreatment of Th2 cells with IL-12 also reversed histamine's effects on IL-13 secretion from stimulatory to inhibitory. These observations suggest a role for PKA and the Jak-STAT pathway in histamine-mediated elevation of IL-13 secretion and transcription.

Original language	English (US)
Pages (from-to)	1923-1937
Number of pages	15
Journal	International Immunopharmacology
Volume	1
Issue number	11
DOIs	https://doi.org/10.1016/S1567-5769(01)00117-5
State	Published - 2001
Externally published	Yes

Keywords

H-8
Histamine
Interleukin-12
Interleukin-13
Janus kinase
Protein kinase A
Rp-cAMPS
STAT6
Th2 lymphocytes
Tyrphostin AG490

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Pharmacology

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10.1016/S1567-5769(01)00117-5

Cite this

@article{51617367ad214feba99bc2fc812c2818,

title = "Regulation of IL-13 production by histamine in cloned murine T helper type 2 cells",

abstract = "Histamine affects the balance of T helper type 1 (Th1) and T helper type 2 (Th2) cytokines by shifting cytokine production from a Th1 to a Th2 pattern. Interleukin-13 (IL-13) is an important autacoid mediator that has been implicated in the development of allergic disease. This study was designed to investigate the mechanisms of regulation of IL-13 by histamine in Th2 cells. D10.G4.1 cells, a murine Th2 cell line, were treated with histamine (10-8-10-4 M) and then activated with PMA (phorbol 12 myristate 13-acetate) plus ionomycin or αCD3. Levels of IL-13 production were then measured by enzyme-linked immunosorbent assay (ELISA) and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Cells were pretreated with histamine receptor antagonists pyrilamine, ranitidine, cimetidine and thioperamide to determine the involvement of histamine receptors. Cells were also pretreated with protein kinase A (PKA) inhibitors N-[2-(methylaminoethyl)]-5-isoquinoline-sulfonamide (H-8) and Rp-diastereomer of adenosine cyclic 3′5′-phosphorothionate (Rp-cAMPS), and Janus kinase-signal transducer and activator of transcription (Jak-STAT) inhibitor tyrphostin AG490 prior to the addition of histamine. H-8 is an inhibitor of the catalytic subunit of PKA while Rp-cAMPS is an inhibitor of the regulatory subunit of PKA. Tyrphostin is an inhibitor of Jak2, Jak3, STAT1, STAT3 and STAT5. Finally, cells were pretreated with IL-12, a monokine known to repress STAT6 DNA binding. We found that histamine dose-dependently enhanced IL-13 secretion and mRNA levels in Th2 cells via H1 and H2 receptors. Pretreatment of cells with H-8, Rp-cAMPS and tyrphostin prevented histamine-induced secretion and transcription of IL-13. Likewise, pretreatment of Th2 cells with IL-12 also reversed histamine's effects on IL-13 secretion from stimulatory to inhibitory. These observations suggest a role for PKA and the Jak-STAT pathway in histamine-mediated elevation of IL-13 secretion and transcription.",

keywords = "H-8, Histamine, Interleukin-12, Interleukin-13, Janus kinase, Protein kinase A, Rp-cAMPS, STAT6, Th2 lymphocytes, Tyrphostin AG490",

author = "Elliott, {Kathleen A.} and Osna, {Natalia A.} and Scofield, {Margaret A.} and Khan, {Manzoor M.}",

note = "Funding Information: This work was supported by grants from the American Lung Association of Nebraska and NIH NIAID (2R15 AI32670-02).",

year = "2001",

doi = "10.1016/S1567-5769(01)00117-5",

language = "English (US)",

volume = "1",

pages = "1923--1937",

journal = "International Immunopharmacology",

issn = "1567-5769",

publisher = "Elsevier B.V.",

number = "11",

}

TY - JOUR

T1 - Regulation of IL-13 production by histamine in cloned murine T helper type 2 cells

AU - Elliott, Kathleen A.

AU - Osna, Natalia A.

AU - Scofield, Margaret A.

AU - Khan, Manzoor M.

N1 - Funding Information: This work was supported by grants from the American Lung Association of Nebraska and NIH NIAID (2R15 AI32670-02).

PY - 2001

Y1 - 2001

N2 - Histamine affects the balance of T helper type 1 (Th1) and T helper type 2 (Th2) cytokines by shifting cytokine production from a Th1 to a Th2 pattern. Interleukin-13 (IL-13) is an important autacoid mediator that has been implicated in the development of allergic disease. This study was designed to investigate the mechanisms of regulation of IL-13 by histamine in Th2 cells. D10.G4.1 cells, a murine Th2 cell line, were treated with histamine (10-8-10-4 M) and then activated with PMA (phorbol 12 myristate 13-acetate) plus ionomycin or αCD3. Levels of IL-13 production were then measured by enzyme-linked immunosorbent assay (ELISA) and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Cells were pretreated with histamine receptor antagonists pyrilamine, ranitidine, cimetidine and thioperamide to determine the involvement of histamine receptors. Cells were also pretreated with protein kinase A (PKA) inhibitors N-[2-(methylaminoethyl)]-5-isoquinoline-sulfonamide (H-8) and Rp-diastereomer of adenosine cyclic 3′5′-phosphorothionate (Rp-cAMPS), and Janus kinase-signal transducer and activator of transcription (Jak-STAT) inhibitor tyrphostin AG490 prior to the addition of histamine. H-8 is an inhibitor of the catalytic subunit of PKA while Rp-cAMPS is an inhibitor of the regulatory subunit of PKA. Tyrphostin is an inhibitor of Jak2, Jak3, STAT1, STAT3 and STAT5. Finally, cells were pretreated with IL-12, a monokine known to repress STAT6 DNA binding. We found that histamine dose-dependently enhanced IL-13 secretion and mRNA levels in Th2 cells via H1 and H2 receptors. Pretreatment of cells with H-8, Rp-cAMPS and tyrphostin prevented histamine-induced secretion and transcription of IL-13. Likewise, pretreatment of Th2 cells with IL-12 also reversed histamine's effects on IL-13 secretion from stimulatory to inhibitory. These observations suggest a role for PKA and the Jak-STAT pathway in histamine-mediated elevation of IL-13 secretion and transcription.

AB - Histamine affects the balance of T helper type 1 (Th1) and T helper type 2 (Th2) cytokines by shifting cytokine production from a Th1 to a Th2 pattern. Interleukin-13 (IL-13) is an important autacoid mediator that has been implicated in the development of allergic disease. This study was designed to investigate the mechanisms of regulation of IL-13 by histamine in Th2 cells. D10.G4.1 cells, a murine Th2 cell line, were treated with histamine (10-8-10-4 M) and then activated with PMA (phorbol 12 myristate 13-acetate) plus ionomycin or αCD3. Levels of IL-13 production were then measured by enzyme-linked immunosorbent assay (ELISA) and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Cells were pretreated with histamine receptor antagonists pyrilamine, ranitidine, cimetidine and thioperamide to determine the involvement of histamine receptors. Cells were also pretreated with protein kinase A (PKA) inhibitors N-[2-(methylaminoethyl)]-5-isoquinoline-sulfonamide (H-8) and Rp-diastereomer of adenosine cyclic 3′5′-phosphorothionate (Rp-cAMPS), and Janus kinase-signal transducer and activator of transcription (Jak-STAT) inhibitor tyrphostin AG490 prior to the addition of histamine. H-8 is an inhibitor of the catalytic subunit of PKA while Rp-cAMPS is an inhibitor of the regulatory subunit of PKA. Tyrphostin is an inhibitor of Jak2, Jak3, STAT1, STAT3 and STAT5. Finally, cells were pretreated with IL-12, a monokine known to repress STAT6 DNA binding. We found that histamine dose-dependently enhanced IL-13 secretion and mRNA levels in Th2 cells via H1 and H2 receptors. Pretreatment of cells with H-8, Rp-cAMPS and tyrphostin prevented histamine-induced secretion and transcription of IL-13. Likewise, pretreatment of Th2 cells with IL-12 also reversed histamine's effects on IL-13 secretion from stimulatory to inhibitory. These observations suggest a role for PKA and the Jak-STAT pathway in histamine-mediated elevation of IL-13 secretion and transcription.

KW - H-8

KW - Histamine

KW - Interleukin-12

KW - Interleukin-13

KW - Janus kinase

KW - Protein kinase A

KW - Rp-cAMPS

KW - STAT6

KW - Th2 lymphocytes

KW - Tyrphostin AG490

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U2 - 10.1016/S1567-5769(01)00117-5

DO - 10.1016/S1567-5769(01)00117-5

M3 - Article

C2 - 11606024

AN - SCOPUS:0034839238

SN - 1567-5769

VL - 1

SP - 1923

EP - 1937

JO - International Immunopharmacology

JF - International Immunopharmacology

IS - 11

ER -

Regulation of IL-13 production by histamine in cloned murine T helper type 2 cells

Abstract

Keywords

ASJC Scopus subject areas

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