Characterization of a conditional interleukin‐1 receptor 1 mouse mutant using the Cre/LoxP system

Abdulaal, Wesam H.; Walker, Catherine; Costello, Ryan; Redondo‐Castro, Elena; Mufazalov, Ilgiz A.; Papaemmanouil, Athina; Rothwell, Nancy J.; Allan, Stuart M.; Waisman, Ari; Pinteaux, Emmanuel; Müller, Werner

doi:10.1002/eji.201546075

Cited by 25 publications

(44 citation statements)

References 14 publications

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“…Myd88 F/F , Tlr4 F/F , Il1r1 F/F and ColVI-cre mice have been previously described ( Abdulaal et al., 2016 , Armaka et al., 2008 , Sodhi et al., 2012 , Vlantis et al., 2016 ). Rosa mTmG and Apc min/+ mice were purchased from the Jackson Laboratory ( Dove et al., 1997 , Muzumdar et al., 2007 ).…”

Section: Methodsmentioning

confidence: 99%

Innate Sensing through Mesenchymal TLR4/MyD88 Signals Promotes Spontaneous Intestinal Tumorigenesis

Koliaraki¹,

Chalkidi²,

Henriques³

et al. 2019

Cell Reports

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SummaryMyD88, an adaptor molecule downstream of innate pathways, plays a significant tumor-promoting role in sporadic intestinal carcinogenesis of the Apcmin/+ model, which carries a mutation in the Apc gene. Here, we show that deletion of MyD88 in intestinal mesenchymal cells (IMCs) significantly reduces tumorigenesis in this model. This phenotype is associated with decreased epithelial cell proliferation, altered inflammatory and tumorigenic immune cell infiltration, and modified gene expression similar to complete MyD88 knockout mice. Genetic deletion of TLR4, but not interleukin-1 receptor (IL-1R), in IMCs led to altered molecular profiles and reduction of intestinal tumors similar to the MyD88 deficiency. Ex vivo analysis in IMCs indicated that these effects could be mediated through downstream signals involving growth factors and inflammatory and extracellular matrix (ECM)-regulating genes, also found in human cancer-associated fibroblasts (CAFs). Our results provide direct evidence that during tumorigenesis, IMCs and CAFs are activated by innate TLR4/MyD88-mediated signals and promote carcinogenesis in the intestine.

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Section: Methodsmentioning

confidence: 99%

Innate Sensing through Mesenchymal TLR4/MyD88 Signals Promotes Spontaneous Intestinal Tumorigenesis

Koliaraki¹,

Chalkidi²,

Henriques³

et al. 2019

Cell Reports

Self Cite

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“…The global IL-1 receptor ( Il1r1 ) KO mouse line was generated by crossing PGK-Cre global deleter mice (The Jackson Laboratory, Bar Harbor, ME, USA) with floxed Il1r1 mice (34) (provided by E. Pinteaux, University of Manchester, Manchester, United Kingdom).…”

Section: Methodsmentioning

confidence: 99%

Cardiac fibroblast‐specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin‐6 signaling mechanism

et al. 2018

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Recent studies suggest that cardiac fibroblast-specific p38α MAPK contributes to the development of cardiac hypertrophy, but the underlying mechanism is unknown. Our study used a novel fibroblast-specific, tamoxifen-inducible p38α knockout (KO) mouse line to characterize the role of fibroblast p38α in modulating cardiac hypertrophy, and we elucidated the mechanism. Myocardial injury was induced in tamoxifen-treated Cre-positive p38α KO mice or control littermates via chronic infusion of the β-adrenergic receptor agonist isoproterenol. Cardiac function was assessed by pressure-volume conductance catheter analysis and was evaluated for cardiac hypertrophy at tissue, cellular, and molecular levels. Isoproterenol infusion in control mice promoted overt cardiac hypertrophy and dysfunction (reduced ejection fraction, increased end systolic volume, increased cardiac weight index, increased cardiomyocyte area, increased fibrosis, and up-regulation of myocyte fetal genes and hypertrophy-associated microRNAs). Fibroblast-specific p38α KO mice exhibited marked protection against myocardial injury, with isoproterenol-induced alterations in cardiac function, histology, and molecular markers all being attenuated. In vitro mechanistic studies determined that cardiac fibroblasts responded to damaged myocardium by secreting several paracrine factors known to induce cardiomyocyte hypertrophy, including IL-6, whose secretion was dependent upon p38α activity. In conclusion, cardiac fibroblast p38α contributes to cardiomyocyte hypertrophy and cardiac dysfunction, potentially via a mechanism involving paracrine fibroblast-to-myocyte IL-6 signaling.-Bageghni, S. A., Hemmings, K. E., Zava, N., Denton, C. P., Porter, K. E., Ainscough, J. F. X., Drinkhill, M. J., Turner, N. A. Cardiac fibroblast-specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin-6 signaling mechanism.

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“…In breast cancer these are primarily bone, lung, and brain with bone being the most prominent (7). We have previously shown that a bone seeking breast cancer cell line, (MDA-IV) produces high concentrations of IL-1B compared to parental MDA-MB-231 cells (2).…”

Section: Tumor Cell Derived Il-1b Predicts Future Breast Cancer Relapmentioning

confidence: 99%

Endogenous Production of IL1B by Breast Cancer Cells Drives Metastasis and Colonization of the Bone Microenvironment

Tulotta

Lefley

Freeman

et al. 2019

Clinical Cancer Research

137

122

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Characterization of a conditional interleukin‐1 receptor 1 mouse mutant using the Cre/LoxP system

Cited by 25 publications

References 14 publications

Innate Sensing through Mesenchymal TLR4/MyD88 Signals Promotes Spontaneous Intestinal Tumorigenesis

Innate Sensing through Mesenchymal TLR4/MyD88 Signals Promotes Spontaneous Intestinal Tumorigenesis

Cardiac fibroblast‐specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin‐6 signaling mechanism

Endogenous Production of IL1B by Breast Cancer Cells Drives Metastasis and Colonization of the Bone Microenvironment

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