Three Promoters Regulate Tissue- and Cell Type-specific Expression of Murine Interleukin-1 Receptor Type I

Chen, Qun; Zhang, Hao; An, Ying; Herkenham, Miles; Lai, Wenmin; Popovich, Phillip G.; Agarwal, Sudha; Quan, Ning

doi:10.1074/jbc.m808261200

Cited by 13 publications

(12 citation statements)

References 30 publications

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“…They are represented in green, purple, blue, and red in Table 1 Three of the clusters (TSS1, TSS2, and TSS3) are in agreement with our previous study (14), although >30 additional bases of the 5′ UTR regions in two of the three clusters were uncovered by the current method. Importantly, a unique fourth TSS cluster was identified.…”

Section: Resultssupporting

confidence: 75%

Interleukin-1R3 mediates interleukin-1–induced potassium current increase through fast activation of Akt kinase

Jiang

Zhu

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Inflammatory cytokine interleukin-1 (IL-1) performs multiple functions in the central nervous system. The type 1 IL-1 receptor (IL-1R1) and the IL-1 receptor accessory protein (IL-1RAcP) form a functional IL-1 receptor complex that is thought to mediate most, if not all, IL-1-induced effects. Several recent studies, however, suggest the existence of a heretofore-unidentified receptor for IL-1. In this study, we report that the IL-1R1 gene contains an internal promoter that drives the transcription of a shortened IL-1R1 mRNA. This mRNA is the template for a unique IL-1R protein that is identical to IL-1R1 at the C terminus, but with a shorter extracellular domain at the N terminus. We have termed this molecule IL-1R3. The mRNA and protein for IL-1R3 are expressed in normal and two strains of commercially available IL-1R1 knockout mice. Western blot analysis shows IL-1R3 is preferentially expressed in neural tissues. Furthermore, IL-1β binds specifically to IL-1R3 when it is complexed with the newly discovered alternative IL-1 receptor accessory protein, IL-1RAcPb. Stimulation of neurons expressing both IL-1R3 and IL1RAcPb with IL-1β causes fast activation of the Akt kinase, which leads to an increase in voltage-gated potassium current. These results demonstrate that IL-1R3/IL-1RAcPb complex mediates a unique subset of IL-1 activity that accounts for many previously unexplained IL-1 effects in the central nervous system. signal transduction | NF-κB | p38

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Section: Resultssupporting

confidence: 75%

Interleukin-1R3 mediates interleukin-1–induced potassium current increase through fast activation of Akt kinase

Jiang

Zhu

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Inspection of the core promoter sequences showed no TATA box consensus sequence in any of the hIL-1R1 promoters. This is consistent with previous reports that IL-1R1 uses TATA-less promoters 15,16. Other studies have demonstrated that TATA-less promoters often start transcription from several TSSs downstream of the promoter 18.…”

Section: Discussionsupporting

confidence: 93%

“…We showed in a recent study, that three different promoters control murine IL-1R1 (mIL-1R1) expression in a tissue- and cell type-specific manner, 15 suggesting that the regulation of IL-1R1 by multiple promoters is an important mechanism for controlling the diverse functions of IL-1R1. Screening transcription start sites of mIL-1R1 from a large panel of different tissue samples was necessary for the discovery of these mIL-1R1 promoters because some promoters are not active in all tissues.…”

Section: Introductionmentioning

confidence: 99%

Existence of seven human IL-1R1 promoters

Quan¹

2010

JIR

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Previous studies have reported the existence of three promoters for the human type I interleukin-1 receptor (hIL-1R1) gene. These promoters were discovered by identifying discrete transcription start sites (TSS) from limited human cell lines. In this study, we examined the TSSs of hIL-1R1 mRNA from 24 different tissues and identified several novel TSSs in hIL-1R1 that suggest the existence of seven hIL-1R1 promoters: three of them are the same as those reported previously and four are putative novel promoters. Using a promoter-reporter assay, we show here that these promoters can drive the transcription of the reporter gene. In addition, these promoters exhibit cell type specific expression patterns and they can be regulated by enhancer elements in a cell type specific manner. Only one of the promoters was found to be sensitive to the stimulation by glucocorticoids. Similar to our recent report on murine IL-1R1, two of the hIL-1R1 promoters appear to be the dominant promoters, one of which was published previously and the other is identified in the present study. We also found an internal promoter that drives the expression of IL-1R1 after the conventional translation start codon, suggesting that a truncated hIL-1R1 may be expressed by this promoter. These results provide additional information regarding the transcription of hIL-1R1.

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“…To this end, we thoroughly investigated the existence of multiple IL-1R1 promoters. Using the sensitive CapFishing method in combination with nested PCR, we ultimately found 4 murine and 7 human IL-1R1 promoters (Chen et al, 2009; Li et al., 2010). In neurons, IL-1R1 in the mouse is driven by two different promoters that are not active in the non-neuronal cell types.…”

Section: The Diverse Sources Targets and Contrasting Functions Of Imentioning

confidence: 99%

“…It is likely that the neurophysiological functions of IL-1 are mediated by neuronal specific IL-1 receptors and their non-inflammatory signaling pathways. Furthermore, in vitro promoter–reporter analysis shows different IL-1R1 promoters are differentially regulated by glucocorticoids, suggesting responsiveness to IL-1 could be differentially regulated in different cell types by modulating hormones (Chen et al, 2009). The distinct cell type specific actions of IL-1 on various CNS cells can also be demonstrated in cultured CNS cell lines (An et al, 2011).…”

Section: The Diverse Sources Targets and Contrasting Functions Of Imentioning

confidence: 99%

In-depth conversation: Spectrum and kinetics of neuroimmune afferent pathways

Quan

2014

Brain, Behavior, and Immunity

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Since my last review on neuroimmune communication afferents in 2008, this area has witnessed substantial growth. At a basic science level, numerous new and exciting phenomena have been described, adding both depth and complexity to the crosstalk between the immune system and the nervous system. At a translational level, accumulating evidence indicates neuroimmune interaction could be a contributing factor for many disease states, as well as an effective physiological mechanism that coordinates the activities of these two systems in healthy individuals or during tissue distress. Furthermore, new evidence suggests neuroimmune interactions are inherently dynamic: varying activities in either the nervous system or the immune system could impact interactions between them. In this review I will attempt to integrate multifarious, and sometimes disparate, findings into a modified conceptual framework that describes the concordance of neuroimmune communication through the cooperative connection between these two systems and the dysfunction that may arise when their inappropriate crosstalk occurs.

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Three Promoters Regulate Tissue- and Cell Type-specific Expression of Murine Interleukin-1 Receptor Type I

Cited by 13 publications

References 30 publications

Interleukin-1R3 mediates interleukin-1–induced potassium current increase through fast activation of Akt kinase

Interleukin-1R3 mediates interleukin-1–induced potassium current increase through fast activation of Akt kinase

Existence of seven human IL-1R1 promoters

In-depth conversation: Spectrum and kinetics of neuroimmune afferent pathways

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