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IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor Stat3

IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor Stat3
IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor Stat3
IL-10 is an important immunosuppressive cytokine that can down-regulate expression of other cytokines and has been shown to down-regulate itself. We show, in this study, that treatment of human monocyte-derived macrophages with IL-10 induces IL-10 mRNA in a dose- and time-dependent manner with an optimum induction at 100 ng/ml and at 6 h, whereas IL-10-induced IL-10 protein can be detected at 18 h. In the same cells, IL-10 can partially suppress IL-10 mRNA induced by LPS, but only down to the level of IL-10-induced IL-10. An adenoviral luciferase reporter construct driven by the ?195 IL-10 promoter, which contains a Stat motif, was readily induced by both IL-10 and LPS. Mutation of this Stat motif ablated IL-10 activation of this promoter, but not the LPS activation. Finally, we show that overexpression of a dominant-negative Stat3 protein will prevent IL-10 induction, but not LPS induction, of IL-10 mRNA. These data show that IL-10 induces IL-10 in monocyte-derived macrophages in an autocrine manner via activation of the transcription factor Stat3
0022-1767
4779-4785
Staples, K.J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Smallie, T.
c47d7cd7-6b4d-4c02-aacc-8706d4c4abbc
Williams, L.M.
94107b02-74d6-4ee6-aea3-92cc713a62d1
Foey, A.
70098a98-afce-45b7-a096-ffbf2ba8ef10
Burke, B.
2cdd32d9-cd1f-4b70-8896-46704f009a0b
Foxwell, B.M.J.
f0a0e75c-b32d-4841-bc07-5415370be3e9
Ziegler-Heitbrock, L.
98b9cb71-55ac-426c-946a-d5b4232926cc
Staples, K.J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Smallie, T.
c47d7cd7-6b4d-4c02-aacc-8706d4c4abbc
Williams, L.M.
94107b02-74d6-4ee6-aea3-92cc713a62d1
Foey, A.
70098a98-afce-45b7-a096-ffbf2ba8ef10
Burke, B.
2cdd32d9-cd1f-4b70-8896-46704f009a0b
Foxwell, B.M.J.
f0a0e75c-b32d-4841-bc07-5415370be3e9
Ziegler-Heitbrock, L.
98b9cb71-55ac-426c-946a-d5b4232926cc

Staples, K.J., Smallie, T., Williams, L.M., Foey, A., Burke, B., Foxwell, B.M.J. and Ziegler-Heitbrock, L. (2007) IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor Stat3. The Journal of Immunology, 178 (8), 4779-4785. (doi:10.4049/?jimmunol.178.8.4779). (PMID:17404258)

Record type: Article

Abstract

IL-10 is an important immunosuppressive cytokine that can down-regulate expression of other cytokines and has been shown to down-regulate itself. We show, in this study, that treatment of human monocyte-derived macrophages with IL-10 induces IL-10 mRNA in a dose- and time-dependent manner with an optimum induction at 100 ng/ml and at 6 h, whereas IL-10-induced IL-10 protein can be detected at 18 h. In the same cells, IL-10 can partially suppress IL-10 mRNA induced by LPS, but only down to the level of IL-10-induced IL-10. An adenoviral luciferase reporter construct driven by the ?195 IL-10 promoter, which contains a Stat motif, was readily induced by both IL-10 and LPS. Mutation of this Stat motif ablated IL-10 activation of this promoter, but not the LPS activation. Finally, we show that overexpression of a dominant-negative Stat3 protein will prevent IL-10 induction, but not LPS induction, of IL-10 mRNA. These data show that IL-10 induces IL-10 in monocyte-derived macrophages in an autocrine manner via activation of the transcription factor Stat3

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Published date: 15 April 2007
Organisations: Faculty of Medicine

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Local EPrints ID: 374398
URI: http://eprints.soton.ac.uk/id/eprint/374398
ISSN: 0022-1767
PURE UUID: 2b17b37f-3a97-4bf9-b9b7-3992a191d797
ORCID for K.J. Staples: ORCID iD orcid.org/0000-0003-3844-6457

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Date deposited: 16 Feb 2015 11:17
Last modified: 10 Dec 2019 01:43

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Contributors

Author: K.J. Staples ORCID iD
Author: T. Smallie
Author: L.M. Williams
Author: A. Foey
Author: B. Burke
Author: B.M.J. Foxwell
Author: L. Ziegler-Heitbrock

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