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

Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene
Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene
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.
0161-5890
3230-3237
Unterberger, Claudia
3faf7a8a-32bd-4770-b793-6f5096a24046
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Smallie, Timothy
af347f5b-3d26-400b-abcd-c7252c5e616a
Williams, Lynn
f2d321b5-92c6-4cc3-b18c-1f8f389aff89
Foxwell, Brian
931331bf-724f-462f-be80-c6c9641a05d0
Schaefer, Annette
f4cff190-394e-4e14-90cd-5186529bd40c
Kempkes, Bettina
ae9c77e6-d527-438a-9f79-ae2121e34830
Hofer, T.P.J.
ab2e4d4d-8a67-4257-b727-adbf53ffc1f6
Koeppel, Max
73da433d-df13-40dc-a00c-c0c59c6218ea
Lohrum, Marion
a358dc72-0837-4d18-b431-dbf9a5f9a439
Stunnenberg, Henk
a7b7ea55-cac3-4761-9dba-18ce0e834f09
Frankenberger, Marion
55dd9ff6-ea3a-479c-a105-2d4fe5cd81ce
Ziegler-Heitbrock, Loems
71bb9dd4-262c-46ba-9c10-1be5941ffca4
Unterberger, Claudia
3faf7a8a-32bd-4770-b793-6f5096a24046
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Smallie, Timothy
af347f5b-3d26-400b-abcd-c7252c5e616a
Williams, Lynn
f2d321b5-92c6-4cc3-b18c-1f8f389aff89
Foxwell, Brian
931331bf-724f-462f-be80-c6c9641a05d0
Schaefer, Annette
f4cff190-394e-4e14-90cd-5186529bd40c
Kempkes, Bettina
ae9c77e6-d527-438a-9f79-ae2121e34830
Hofer, T.P.J.
ab2e4d4d-8a67-4257-b727-adbf53ffc1f6
Koeppel, Max
73da433d-df13-40dc-a00c-c0c59c6218ea
Lohrum, Marion
a358dc72-0837-4d18-b431-dbf9a5f9a439
Stunnenberg, Henk
a7b7ea55-cac3-4761-9dba-18ce0e834f09
Frankenberger, Marion
55dd9ff6-ea3a-479c-a105-2d4fe5cd81ce
Ziegler-Heitbrock, Loems
71bb9dd4-262c-46ba-9c10-1be5941ffca4

Unterberger, Claudia, Staples, Karl J., Smallie, Timothy, Williams, Lynn, Foxwell, Brian, Schaefer, Annette, Kempkes, Bettina, Hofer, T.P.J., Koeppel, Max, Lohrum, Marion, Stunnenberg, Henk, Frankenberger, Marion and Ziegler-Heitbrock, Loems (2008) Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene. Molecular Immunology, 45 (11), 3230-3237. (doi:10.1016/j.molimm.2008.02.020). (PMID:18403020)

Record type: Article

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.

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Published date: June 2008

Identifiers

Local EPrints ID: 185833
URI: http://eprints.soton.ac.uk/id/eprint/185833
ISSN: 0161-5890
PURE UUID: 5a6a3004-33dd-4e69-b063-e7288a5b775d
ORCID for Karl J. Staples: ORCID iD orcid.org/0000-0003-3844-6457

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Date deposited: 11 May 2011 10:16
Last modified: 15 Mar 2024 03:27

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Contributors

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

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