Disease relevance of Il1r1

• Moreover, hepatic adenomas from mice chronically exposed to Wy-14 643 had increased expression of Il1beta, Il1r1, Il6, and Ppargamma1 [1].
• The specificity of the block is illustrated by the fact that K5-IkappaBalpha mice lacking the IL-1 receptor type 1 (Il1r1) develop inflammation and squamous cell carcinomas [2].
• HSV-1-mediated IL-1 receptor antagonist gene therapy ameliorates MOG(35-55)-induced experimental autoimmune encephalomyelitis in C57BL/6 mice [3].
• In a model of mild asthma, based on repeated sensitization of mice with low doses of ovalbumin in the absence of any adjuvant and multiple intranasal challenges, the pulmonary eosinophilic inflammation and goblet cell hyperplasia were strongly reduced in IL-1R1(-/-) as compared to control BALB/c mice [4].
• In the current studies, we investigated whether MyD88, the primary, but not exclusive, intracellular signal transduction pathway for Toll-like receptor 4 and IL-1 receptor I, is necessary for anorexia and weight loss to occur in response to stimuli that activate these key innate immune receptors [5].

Psychiatry related information on Il1r1

• To assess the potential role of IL-1, we tested the ability of a naturally occurring IL-1-receptor antagonist (IL-1ra) to antagonize the changes in feeding behavior induced by IL-1, endotoxin (lipopolysaccharide, LPS), and infection with influenza virus [6].
• Several perturbations in host defense mechanisms were detected in the lungs of IL-1R(-/-) mice [7].
• Significant differences in brain morphology and expression of cytokine IL-1 beta, type I IL-1 receptor, and erythropoietin receptor genes in brain cells were detected in (CBA x C57Bl/6)F1 mice with different initial levels of orientation and exploratory behavior [8].

High impact information on Il1r1

• A VV open reading frame (ORF) that exhibits 30% amino acid identity to the type II IL-1 receptor was expressed in CV-1-EBNA cells and shown specifically to bind mIL-1 beta [9].
• The product of the cloned complementary DNA binds both IL-1 alpha and IL-1 beta in a manner indistinguishable from that of the native T cell IL-1 receptor [10].
• IL-1 receptor (IL-1R)/Toll-like receptor (TLR) family and TNF receptor (TNFR) superfamily members are critical for regulating multiple aspects of dendritic cell (DC) biology [11].
• We show that the induction of antigen-specific ThIL-17 cells, but not T helper (Th)1 or Th2 cells, by immunization with antigens and adjuvants is abrogated in IL-1 receptor type I-deficient (IL-1RI(-/-)) mice [12].
• The administration of a TLR-4 ligand, lipopolysaccharide, concomitant with arthritogenic serum in IL-1 receptor-deficient mice resulted in acute paw swelling, but not in MyD88-deficient mice [13].

Chemical compound and disease context of Il1r1

• In acute dextran sulfate sodium-induced colitis, ICE-deficient (ICE KO) mice exhibited a greater than 50% decrease of the clinical scores weight loss, diarrhea, rectal bleeding, and colon length, whereas daily treatment with IL-1 receptor antagonist revealed a modest reduction in colitis severity [14].
• Curcumin blocks interleukin-1 (IL-1) signaling by inhibiting the recruitment of the IL-1 receptor-associated kinase IRAK in murine thymoma EL-4 cells [15].
• IL-1 receptor blockade quite significantly diminished lung tissue damage and granuloma formation, judging from morphometric index and lung hydroxyproline measurements [16].
• Resistance to Pseudomonas aeruginosa Chronic Lung Infection Requires Cystic Fibrosis Transmembrane Conductance Regulator-Modulated Interleukin-1 (IL-1) Release and Signaling through the IL-1 Receptor [17].
• To determine the relative in vivo importance of IL-1 release after allergen challenge to the subsequent endothelial adhesion and recruitment of eosinophils, the authors used ovalbumin sensitization and inhalation challenge to induce airway eosinophilia in IL-1 receptor type 1-deficient and control wild-type mice [18].

Biological context of Il1r1

• Interleukin-1 (IL-1) directly and indirectly promotes hematopoietic cell growth through type I IL-1 receptor [19].
• Moreover, priming of CD4(+) T cells in bronchial lymph nodes and their recruitment to the lung was affected in IL-1R1(-/-) mice associated with impaired antibody responses including IgG, IgE, and IgA [4].
• The murine Il-1r1 gene has thus been separated from the IL-1 genes, which lie on murine chromosome 2 [20].
• Differential gene expression for IL-1 receptor antagonist, IL-1, and TNF receptors and IL-1 and TNF synthesis may explain IL-1-induced resistance to infection [21].
• Early response cytokines and innate immunity: essential roles for TNF receptor 1 and type I IL-1 receptor during Escherichia coli pneumonia in mice [22].

Anatomical context of Il1r1

• In contrast, tumorigenesis remained unaffected in either compound mutants of K19-C2mE containing Il1r1 or Rag2 mutation, indicating that neither interleukin-1beta signaling nor T cell/B cell response was required for the development of hyperplastic tumors [23].
• At the highest dose (500 micrograms), significant decreases in osteoclast number occurred in mutant mice compared to wild-type mice: (i) a 64% reduction for the TNF p55(-/-)/IL-1R(-/-) mice, (ii) a 57% reduction for the IL-1R(-/-) mice, (iii) a 41% reduction for the TNF p55(-/-)/p75(-/-) mice, and (iv) a 38% reduction for the ICE(-/-) mice [24].
• Influx of neutrophils was decreased in bronchoalveolar lavage fluids in IL-1R -/- mice compared with wild-type mice [25].
• The absence of the IL-1 signal attenuated the outgrowth of Pseudomonas in lungs, as reflected by an increasing number of colony-forming units (cfu) during Pseudomonas pneumonia in wild-type mice and a concurrently decreasing number of cfu during pulmonary infection in IL-1R -/- mice (P < 0.05, IL-1R -/- mice vs. wild-type mice) [25].
• Thus, IL-1R1 appears to be important for the recruitment of leukocytes across the blood-brain barrier [26].

Associations of Il1r1 with chemical compounds

• In addition, anti-IL-1 receptor, type 1/p80 (IL-1R) antibodies were able to abrogate the response to nafenopin [27].
• To assess the role of IL-1 receptor type I (IL-1RI) in the sickness-inducing effects of IL-1, IL-1beta and the cytokine inducer lipopolysaccharide were administered to IL-1RI-deficient mice (IL-1RI-/-) [28].
• The increase at 2 h was confirmed by Northern blot analysis and was not prevented by latex occlusion performed immediately after tape-stripping mRNAs for the IL-1 (p80) receptor and TNF (p75) receptor were not detected in epidermis [29].
• The analog also showed agonist activity as assayed by increased prostaglandin E2 synthesis from CHO cells expressing recombinant mouse IL-1 receptor [30].
• Similar to IL-1, IL-6-mediated neuroprotection is also antagonized by pretreatment with IL-1 receptor antagonist and it is not affected by nicotine [31].

Physical interactions of Il1r1

• Furthermore, Shp-2 tyrosine phosphatase was detected in complexes with IKK as well as with IL-1 receptor [32].
• Biacore experiments demonstrated that Hu007 and the type-I IL-1 receptor competed for binding to IL-1beta [33].

Regulatory relationships of Il1r1

• Thus, IL-1 alpha directly and indirectly stimulates the growth and differentiation of purified progenitors through the type I IL-1R but not the type II IL-1R [19].
• Also, there may be a TLR2-specific, MyD88-independent IL-1 receptor/TLR-mediated pathway to activate NF-kappa B in the host defense against mycobacterial infection [34].
• Neuroprotection provided by IL-1 is distinct from TNF-alpha because it is inhibited by IL-1 receptor antagonist; it is not antagonized by nicotine, but it is inhibited by a neutralizing Ab to nerve growth factor (NGF) [31].
• Because IL-1 also stimulates the hypothalamic pituitary-adrenal axis resulting in the production of glucocorticoids (GC), we assessed whether in vivo treatment with HGF and glucocorticoids upregulates IL-1R [35].
• Interleukin 4 (IL) 4 up-regulates gene and surface IL 1 receptor type I in murine T helper type 2 cells [36].

Other interactions of Il1r1

• Furthermore, IL-1 receptor signaling appears to be slightly more important than TNF receptor signaling [24].
• Induction of IL-6 and activation of the HPAA are dependent upon prior activation of an IL-1 type I receptor, as both are inhibited in type I IL-1 receptor-deficient mice [37].
• Semi-quantitative, reverse transcriptase polymerase chain reaction analysis revealed that wild type mice acutely exposed to Wy-14 643 had increased hepatic expression of Il1beta, Il1r1, Hnf4, and Stat3 genes [1].
• Leukocyte infiltration induced by icv IFN-gamma and TNF-alpha was also abrogated in IL-1R1-knockout animals [26].
• A significant decrease in in vitro proliferation of partially purified splenocytes in the presence of ConA was associated with a decrease in IFN-gamma production in the culture supernatants and an increase in IL-1 receptor expression on the cell surface (p<0.05) [38].

Analytical, diagnostic and therapeutic context of Il1r1

• Wild-type and IL-1 receptor I-knockout (IL-1RI(-/-)) mice were exposed to 90 minutes of partial hepatic ischemia and up to 24 hours of reperfusion [39].
• Intracerebroventricular pretreatment with IL-1 receptor antagonist (4 microgram/mouse) attenuated LPS-induced depression of food intake and totally blocked the LPS-induced enhanced expression of proinflammatory cytokine mRNA measured in the hypothalamus 1 h after treatment [40].
• Anti-type 1 IL-1 receptor (R) mAbs also visualized these receptors by flow cytometry on freshly isolated epidermal dendritic cells [41].
• Since IL-1 desensitization is initiated under conditions of low receptor occupancy, it is likely that receptor desensitization results from alterations to a receptor-proximal transducer, rather than from direct modification of the IL-1 receptor [42].
• An S1 nuclease protection assay demonstrated that T cells and fibroblasts contain identical IL-1 receptor mRNA but that pre-B cells and macrophages do not contain this receptor mRNA [43].

References