NF-κB and STAT5 play important roles in the regulation of mouse toll-like receptor 2 gene expression

T. Musikacharoen, T. Matsuguchi, T. Kikuchi, Y. Yoshikai

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Toll-like receptor 2 (TLR2) is involved in the innate immunity by recognizing various bacterial components. We have previously reported that TLR2 gene expression is rapidly induced by LPS or inflammatory cytokines in macrophages, and by TCR engagement or IL-2/IL-15 stimulation in T cells. Here, to investigate the mechanisms governing TER2 transcription, we cloned the 5′ upstream region of the mouse TLR2 (mTLR2) gene and mapped its transcriptional start site. The 5′ upstream region of the mTLR2 gene contains two NF-κB, two CCAAT/enhancer binding protein, one cAMP response element-binding protein, and one STAT consensus sequences. In mouse macrophage cell lines, deletion of both NF-κB sites caused the complete loss of mTLR2 promoter responsiveness to TNF-α. NF-κB sites were also important but not absolutely necessary for LPS-mediated mTLR2 promoter activation. In T cell lines, mTLR2 responsiveness to IL-15 was abrogated by the 3′ NF-κB mutation, whereas 5′ NF-κB showed no functional significance. The STAT binding site also seemed to contribute, as the deletion of this sequence significantly reduced the IL-15-mediated mTLR2 promoter activation. EMSAs confirmed nuclear protein binding to both NF-κB sites in macrophages following LPS and TNF-α stimulation and to the 3′ NF-κB site in T cells after IL-15 treatment. Thus, NF-κB activation is important but differently involved in the regulation of mTLR2 gene expression in macrophages and T cells following LPS or cytokine stimulation.

Original languageEnglish
Pages (from-to)4516-4524
Number of pages9
JournalJournal of Immunology
Volume166
Issue number7
Publication statusPublished - Apr 1 2001
Externally publishedYes

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Interleukin-15
Gene Expression
Macrophages
T-Lymphocytes
Toll-Like Receptor 2
CCAAT-Enhancer-Binding Proteins
Cytokines
Cell Line
Cyclic AMP Response Element-Binding Protein
Sequence Deletion
Consensus Sequence
Nuclear Proteins
Mouse Tlr2 protein
Innate Immunity
Protein Binding
Genes
Interleukin-2
Binding Sites
Mutation

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Musikacharoen, T., Matsuguchi, T., Kikuchi, T., & Yoshikai, Y. (2001). NF-κB and STAT5 play important roles in the regulation of mouse toll-like receptor 2 gene expression. Journal of Immunology, 166(7), 4516-4524.

NF-κB and STAT5 play important roles in the regulation of mouse toll-like receptor 2 gene expression. / Musikacharoen, T.; Matsuguchi, T.; Kikuchi, T.; Yoshikai, Y.

In: Journal of Immunology, Vol. 166, No. 7, 01.04.2001, p. 4516-4524.

Research output: Contribution to journalArticle

Musikacharoen, T, Matsuguchi, T, Kikuchi, T & Yoshikai, Y 2001, 'NF-κB and STAT5 play important roles in the regulation of mouse toll-like receptor 2 gene expression', Journal of Immunology, vol. 166, no. 7, pp. 4516-4524.
Musikacharoen T, Matsuguchi T, Kikuchi T, Yoshikai Y. NF-κB and STAT5 play important roles in the regulation of mouse toll-like receptor 2 gene expression. Journal of Immunology. 2001 Apr 1;166(7):4516-4524.
Musikacharoen, T. ; Matsuguchi, T. ; Kikuchi, T. ; Yoshikai, Y. / NF-κB and STAT5 play important roles in the regulation of mouse toll-like receptor 2 gene expression. In: Journal of Immunology. 2001 ; Vol. 166, No. 7. pp. 4516-4524.
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