Heinz, Sven and Haehnel, Viola and Karaghiosoff, Marina and Schwarzfischer, Lucia and Mueller, Mathias and Krause, Stefan W. and Rehli, Michael (2003) Species-specific regulation of Toll-like receptor 3 genes in men and mice. JOURNAL OF BIOLOGICAL CHEMISTRY, 278 (24). pp. 21502-21509. ISSN 0021-9258
Full text not available from this repository.Abstract
Toll- like receptor 3 ( TLR3) belongs to a family of evolutionary conserved innate immune recognition molecules and recognizes double- stranded RNA, a molecular pattern associated with viral infections. Earlier studies suggested a differential expression pattern in men and mice; the molecular basis for this observation, however, was unknown. Here we demonstrate that species- specific differences in tissue expression and responses to lipopolysaccaride ( LPS) coincide with the presence of different, evolutionary non- conserved promoter sequences in both species. Despite the overall unrelatedness of TLR3 promoter sequences, mRNA expression of both TLR3 orthologues was induced by interferons, particularly by interferon ( IFN)-beta. The basal and IFN-beta-induced activation of promoters from both species largely depended on similar interferon regulatory factor ( IRF) elements, which constitutively bound IRF- 2 and recruited IRF- 1 after stimulation. In murine macrophages, IFN-beta-induced TLR3 up- regulation required IFNAR1, STAT1, and in part IRF- 1, but not the Janus kinase ( Jak) family member Tyk2. We also show that LPS specifically up- regulates TLR3 expression in murine cells through the induction of autocrine/ paracrine IFN-beta. In humans, however, IFN-beta-induced up- regulation of TLR3 was blocked by pretreatment with LPS, despite the efficient induction of IRF- 1. Our findings reveal a mechanistic basis for the observed differences as well as similarities in TLR3 expression in men and mice. The IFN-beta- TLR3 link further suggests a role of TLR3 in innate and adaptive immune responses to viral infections. It will be interesting and important to clarify whether the observed differences in the transcriptional regulation of TLR3 influence innate immune responses in a species- specific manner.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DOUBLE-STRANDED-RNA; DENDRITIC CELLS; TARGETED DISRUPTION; INTERFERON-BETA; EXPRESSION; MACROPHAGES; INDUCTION; ACTIVATION; DEFENSE; FAMILY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Aug 2021 05:01 |
| Last Modified: | 11 Aug 2021 05:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/38899 |
Actions (login required)
 |
View Item |
