Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene

Claudia Unterberger; Karl J. Staples; Timothy Smallie; Lynn Williams; Brian Foxwell; Annette Schaefer; Bettina Kempkes; T. P.J. Hofer; Max Koeppel; Marion Lohrum; Henk Stunnenberg; Marion Frankenberger; Loems Ziegler-Heitbrock

doi:10.1016/j.molimm.2008.02.020

Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene

Claudia Unterberger
, Karl J. Staples
, Timothy Smallie
, Lynn Williams
, Brian Foxwell
, Annette Schaefer
, Bettina Kempkes
, T. P.J. Hofer
, Max Koeppel
, Marion Lohrum
, Henk Stunnenberg
, Marion Frankenberger
, Loems Ziegler-Heitbrock

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

40 Citations (Scopus)

Abstract

In the present report we have determined the molecular mechanisms, which govern the expression of the human IL-10 gene when induced by the glucocorticoid Methyl-Prednisolone (MP). Treatment of cells with MP at 10^-6 M will readily induce IL-10 in CD19+ primary B cells and in a human B cell line. Analysis of the IL-10 promoter showed a robust 18-fold induction and demonstrated that a potential GRE motif was not required, while mutation of the -120 STAT-motif strongly reduced MP-induced trans-activation. A strong induction was also seen with a trimeric STAT-motif and over-expression of dominant-negative STAT3 could block MP induction of IL-10 mRNA. Finally, MP treatment induced binding of STAT3 to the promoter as shown by gelshift, supershift and by chromatin-immunoprecipitation. These data show that glucocorticoid-induced expression of the IL-10 gene is mediated by the transcription factor STAT3.

Original language	English
Pages (from-to)	3230-3237
Number of pages	8
Journal	Molecular Immunology
Volume	45
Issue number	11
DOIs	https://doi.org/10.1016/j.molimm.2008.02.020
Publication status	Published - Jun 2008
Externally published	Yes

Keywords

B cells
Cytokines
Human
Inflammation
Transcription factors

Access to Document

10.1016/j.molimm.2008.02.020

Cite this

Unterberger, C., Staples, K. J., Smallie, T., Williams, L., Foxwell, B., Schaefer, A., Kempkes, B., Hofer, T. P. J., Koeppel, M., Lohrum, M., Stunnenberg, H., Frankenberger, M., & Ziegler-Heitbrock, L. (2008). Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene. Molecular Immunology, 45(11), 3230-3237. https://doi.org/10.1016/j.molimm.2008.02.020

@article{e2d21c37274b4512ba8e975b3987020c,

title = "Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene",

abstract = "In the present report we have determined the molecular mechanisms, which govern the expression of the human IL-10 gene when induced by the glucocorticoid Methyl-Prednisolone (MP). Treatment of cells with MP at 10-6 M will readily induce IL-10 in CD19+ primary B cells and in a human B cell line. Analysis of the IL-10 promoter showed a robust 18-fold induction and demonstrated that a potential GRE motif was not required, while mutation of the -120 STAT-motif strongly reduced MP-induced trans-activation. A strong induction was also seen with a trimeric STAT-motif and over-expression of dominant-negative STAT3 could block MP induction of IL-10 mRNA. Finally, MP treatment induced binding of STAT3 to the promoter as shown by gelshift, supershift and by chromatin-immunoprecipitation. These data show that glucocorticoid-induced expression of the IL-10 gene is mediated by the transcription factor STAT3.",

keywords = "B cells, Cytokines, Human, Inflammation, Transcription factors",

author = "Claudia Unterberger and Staples, \{Karl J.\} and Timothy Smallie and Lynn Williams and Brian Foxwell and Annette Schaefer and Bettina Kempkes and Hofer, \{T. P.J.\} and Max Koeppel and Marion Lohrum and Henk Stunnenberg and Marion Frankenberger and Loems Ziegler-Heitbrock",

note = "Funding Information: This work was supported by grants from Deutsche Forschungsgemeinschaft (FR 1454/2-1), Germany, KWF KUN 2003-2926 (The Netherlands, and BBSRC (91-C19230), UK.",

year = "2008",

month = jun,

doi = "10.1016/j.molimm.2008.02.020",

language = "English",

volume = "45",

pages = "3230--3237",

journal = "Molecular Immunology",

issn = "0161-5890",

publisher = "Elsevier Ltd.",

number = "11",

}

TY - JOUR

T1 - Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene

AU - Unterberger, Claudia

AU - Staples, Karl J.

AU - Smallie, Timothy

AU - Williams, Lynn

AU - Foxwell, Brian

AU - Schaefer, Annette

AU - Kempkes, Bettina

AU - Hofer, T. P.J.

AU - Koeppel, Max

AU - Lohrum, Marion

AU - Stunnenberg, Henk

AU - Frankenberger, Marion

AU - Ziegler-Heitbrock, Loems

N1 - Funding Information: This work was supported by grants from Deutsche Forschungsgemeinschaft (FR 1454/2-1), Germany, KWF KUN 2003-2926 (The Netherlands, and BBSRC (91-C19230), UK.

PY - 2008/6

Y1 - 2008/6

N2 - In the present report we have determined the molecular mechanisms, which govern the expression of the human IL-10 gene when induced by the glucocorticoid Methyl-Prednisolone (MP). Treatment of cells with MP at 10-6 M will readily induce IL-10 in CD19+ primary B cells and in a human B cell line. Analysis of the IL-10 promoter showed a robust 18-fold induction and demonstrated that a potential GRE motif was not required, while mutation of the -120 STAT-motif strongly reduced MP-induced trans-activation. A strong induction was also seen with a trimeric STAT-motif and over-expression of dominant-negative STAT3 could block MP induction of IL-10 mRNA. Finally, MP treatment induced binding of STAT3 to the promoter as shown by gelshift, supershift and by chromatin-immunoprecipitation. These data show that glucocorticoid-induced expression of the IL-10 gene is mediated by the transcription factor STAT3.

AB - In the present report we have determined the molecular mechanisms, which govern the expression of the human IL-10 gene when induced by the glucocorticoid Methyl-Prednisolone (MP). Treatment of cells with MP at 10-6 M will readily induce IL-10 in CD19+ primary B cells and in a human B cell line. Analysis of the IL-10 promoter showed a robust 18-fold induction and demonstrated that a potential GRE motif was not required, while mutation of the -120 STAT-motif strongly reduced MP-induced trans-activation. A strong induction was also seen with a trimeric STAT-motif and over-expression of dominant-negative STAT3 could block MP induction of IL-10 mRNA. Finally, MP treatment induced binding of STAT3 to the promoter as shown by gelshift, supershift and by chromatin-immunoprecipitation. These data show that glucocorticoid-induced expression of the IL-10 gene is mediated by the transcription factor STAT3.

KW - B cells

KW - Cytokines

KW - Human

KW - Inflammation

KW - Transcription factors

UR - https://www.scopus.com/pages/publications/43449100316

U2 - 10.1016/j.molimm.2008.02.020

DO - 10.1016/j.molimm.2008.02.020

M3 - Article

C2 - 18403020

AN - SCOPUS:43449100316

SN - 0161-5890

VL - 45

SP - 3230

EP - 3237

JO - Molecular Immunology

JF - Molecular Immunology

IS - 11

ER -

Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene

Abstract

Keywords

Access to Document

Fingerprint

Cite this