ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance.

Hdl Handle:
http://hdl.handle.net/10147/201259
Title:
ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance.
Authors:
Liu, Jinghua; Buckley, Julliette M; Redmond, H Paul; Wang, Jiang Huai
Affiliation:
Department of Academic Surgery, University College Cork/National University of Ireland, Cork University Hospital, Cork, Ireland.
Citation:
ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance. 2010, 184 (10):5802-8 J. Immunol.
Journal:
Journal of immunology (Baltimore, Md. : 1950)
Issue Date:
15-May-2010
URI:
http://hdl.handle.net/10147/201259
DOI:
10.4049/jimmunol.0904127
PubMed ID:
20400705
Additional Links:
http://www.jimmunol.org/content/184/10/5802.full.pdf+html
Abstract:
Activation of TLR signaling is critical for host innate immunity against bacterial infection. Previous studies reported that the ST2 receptor, a member of the Toll/IL-1 receptor superfamily, functions as a negative regulator of TLR4 signaling and maintains LPS tolerance. However, it is undetermined whether ST2 negatively regulates TLR2 signaling and furthermore, whether a TLR2 agonist, bacterial lipoprotein (BLP)-induced tolerance is dependent on ST2. In this study, we show that BLP stimulation-induced production of proinflammatory cytokines and immunocomplex formation of TLR2-MyD88 and MyD88-IL-1R-associated kinase (IRAK) were significantly enhanced in ST2-deficient macrophages compared with those in wild-type controls. Furthermore, overexpression of ST2 dose-dependently attenuated BLP-induced NF-kappaB activation, suggesting a negative regulatory role of ST2 in TLR2 signaling. A moderate but significantly attenuated production of TNF-alpha and IL-6 on a second BLP stimulation was observed in BLP-pretreated, ST2-deficient macrophages, which is associated with substantially reduced IRAK-1 protein expression and downregulated TLR2-MyD88 and MyD88-IRAK immunocomplex formation. ST2-deficient mice, when pretreated with a nonlethal dose of BLP, benefitted from an improved survival against a subsequent lethal BLP challenge, indicating BLP tolerance develops in the absence of the ST2 receptor. Taken together, our results demonstrate that ST2 acts as a negative regulator of TLR2 signaling, but is not required for BLP-induced tolerance.
Item Type:
Article
Language:
en
Description:
Activation of TLR signaling is critical for host innate immunity against bacterial infection. Previous studies reported that the ST2 receptor, a member of the Toll/IL-1 receptor superfamily, functions as a negative regulator of TLR4 signaling and maintains LPS tolerance. However, it is undetermined whether ST2 negatively regulates TLR2 signaling and furthermore, whether a TLR2 agonist, bacterial lipoprotein (BLP)-induced tolerance is dependent on ST2. In this study, we show that BLP stimulation-induced production of proinflammatory cytokines and immunocomplex formation of TLR2-MyD88 and MyD88-IL-1R-associated kinase (IRAK) were significantly enhanced in ST2-deficient macrophages compared with those in wild-type controls. Furthermore, overexpression of ST2 dose-dependently attenuated BLP-induced NF-kappaB activation, suggesting a negative regulatory role of ST2 in TLR2 signaling. A moderate but significantly attenuated production of TNF-alpha and IL-6 on a second BLP stimulation was observed in BLP-pretreated, ST2-deficient macrophages, which is associated with substantially reduced IRAK-1 protein expression and downregulated TLR2-MyD88 and MyD88-IRAK immunocomplex formation. ST2-deficient mice, when pretreated with a nonlethal dose of BLP, benefitted from an improved survival against a subsequent lethal BLP challenge, indicating BLP tolerance develops in the absence of the ST2 receptor. Taken together, our results demonstrate that ST2 acts as a negative regulator of TLR2 signaling, but is not required for BLP-induced tolerance.
MeSH:
Animals; Bacterial Proteins; Cells, Cultured; Down-Regulation; Humans; Immune Tolerance; Lipoproteins; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Mice, Knockout; Receptors, Interleukin; Signal Transduction; Toll-Like Receptor 2
ISSN:
1550-6606

Full metadata record

DC FieldValue Language
dc.contributor.authorLiu, Jinghuaen
dc.contributor.authorBuckley, Julliette Men
dc.contributor.authorRedmond, H Paulen
dc.contributor.authorWang, Jiang Huaien
dc.date.accessioned2012-01-10T14:43:14Z-
dc.date.available2012-01-10T14:43:14Z-
dc.date.issued2010-05-15-
dc.identifier.citationST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance. 2010, 184 (10):5802-8 J. Immunol.en
dc.identifier.issn1550-6606-
dc.identifier.pmid20400705-
dc.identifier.doi10.4049/jimmunol.0904127-
dc.identifier.urihttp://hdl.handle.net/10147/201259-
dc.descriptionActivation of TLR signaling is critical for host innate immunity against bacterial infection. Previous studies reported that the ST2 receptor, a member of the Toll/IL-1 receptor superfamily, functions as a negative regulator of TLR4 signaling and maintains LPS tolerance. However, it is undetermined whether ST2 negatively regulates TLR2 signaling and furthermore, whether a TLR2 agonist, bacterial lipoprotein (BLP)-induced tolerance is dependent on ST2. In this study, we show that BLP stimulation-induced production of proinflammatory cytokines and immunocomplex formation of TLR2-MyD88 and MyD88-IL-1R-associated kinase (IRAK) were significantly enhanced in ST2-deficient macrophages compared with those in wild-type controls. Furthermore, overexpression of ST2 dose-dependently attenuated BLP-induced NF-kappaB activation, suggesting a negative regulatory role of ST2 in TLR2 signaling. A moderate but significantly attenuated production of TNF-alpha and IL-6 on a second BLP stimulation was observed in BLP-pretreated, ST2-deficient macrophages, which is associated with substantially reduced IRAK-1 protein expression and downregulated TLR2-MyD88 and MyD88-IRAK immunocomplex formation. ST2-deficient mice, when pretreated with a nonlethal dose of BLP, benefitted from an improved survival against a subsequent lethal BLP challenge, indicating BLP tolerance develops in the absence of the ST2 receptor. Taken together, our results demonstrate that ST2 acts as a negative regulator of TLR2 signaling, but is not required for BLP-induced tolerance.en
dc.description.abstractActivation of TLR signaling is critical for host innate immunity against bacterial infection. Previous studies reported that the ST2 receptor, a member of the Toll/IL-1 receptor superfamily, functions as a negative regulator of TLR4 signaling and maintains LPS tolerance. However, it is undetermined whether ST2 negatively regulates TLR2 signaling and furthermore, whether a TLR2 agonist, bacterial lipoprotein (BLP)-induced tolerance is dependent on ST2. In this study, we show that BLP stimulation-induced production of proinflammatory cytokines and immunocomplex formation of TLR2-MyD88 and MyD88-IL-1R-associated kinase (IRAK) were significantly enhanced in ST2-deficient macrophages compared with those in wild-type controls. Furthermore, overexpression of ST2 dose-dependently attenuated BLP-induced NF-kappaB activation, suggesting a negative regulatory role of ST2 in TLR2 signaling. A moderate but significantly attenuated production of TNF-alpha and IL-6 on a second BLP stimulation was observed in BLP-pretreated, ST2-deficient macrophages, which is associated with substantially reduced IRAK-1 protein expression and downregulated TLR2-MyD88 and MyD88-IRAK immunocomplex formation. ST2-deficient mice, when pretreated with a nonlethal dose of BLP, benefitted from an improved survival against a subsequent lethal BLP challenge, indicating BLP tolerance develops in the absence of the ST2 receptor. Taken together, our results demonstrate that ST2 acts as a negative regulator of TLR2 signaling, but is not required for BLP-induced tolerance.-
dc.language.isoenen
dc.relation.urlhttp://www.jimmunol.org/content/184/10/5802.full.pdf+htmlen
dc.subject.meshAnimals-
dc.subject.meshBacterial Proteins-
dc.subject.meshCells, Cultured-
dc.subject.meshDown-Regulation-
dc.subject.meshHumans-
dc.subject.meshImmune Tolerance-
dc.subject.meshLipoproteins-
dc.subject.meshMacrophages, Peritoneal-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshMice, Knockout-
dc.subject.meshReceptors, Interleukin-
dc.subject.meshSignal Transduction-
dc.subject.meshToll-Like Receptor 2-
dc.titleST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance.en
dc.typeArticleen
dc.contributor.departmentDepartment of Academic Surgery, University College Cork/National University of Ireland, Cork University Hospital, Cork, Ireland.en
dc.identifier.journalJournal of immunology (Baltimore, Md. : 1950)en
dc.description.provinceMunster-

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