Abstract
Interleukin-1 receptor antagonist (IL-1ra) is an inhibitor of the proinflammatory IL-1. The IL-1ra gene (Il1rn) maps near the allergen-induced bronchial hyper-responsiveness-1 locus, Abhr1, which we previously mapped to murine chromosome 2 using A/J (asthma susceptible) and C3H/HeJ (asthma resistant) mice. We evaluated the role of Il1rn in our mouse model by comparing its genomic sequence between A/J and C3H/HeJ mice as well as assessing strain-specific RNA and protein production in response to allergen. We identified no functional sequence variations in the Il1rn gene between A/J and C3H/HeJ mice. Il1rn mRNA and protein were induced by ovalbumin (OVA) exposure in both strains, but to a greater extent in A/J mice at the earlier time points. We examined other IL-1 family members (Il1a, Il1b, Il1f9, and Il1r2) and found OVA-induced expression increases at 6 h, yet only Il1b and Il1f9 had strain-specific differences. Of these, only Il1f9 is located within Abhr1, and we found several non-coding polymorphisms in the Il1f9 gene between A/J and C3H/HeJ mice. Our results exclude Il1rn as the gene for Abhr1 and indicate that Il1f9 warrants further investigation based on genetic and expression differences observed in our mouse model of allergic asthma.
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References
Arend, WP (2002) The balance between IL-1 and IL-1Ra in disease. Cytokine Growth Factor Rev 13(4–5):323–340
Arend WP, Guthridge CJ (2000) Biological role of interleukin 1 receptor antagonist isoforms. Ann Rheum Dis 59 (Suppl 1):i60–i64
Arend WP, Malyak M et al (1998) Interleukin-1 receptor antagonist: role in biology. Annu Rev Immunol 16:27–55
Das J, Chen CH et al (2001) A critical role for NF-kappa B in GATA3 expression and TH2 differentiation in allergic airway inflammation. Nat Immunol 2(1):45-50
Debets RJ, Timans C et al (2001) Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2. J Immunol 167(3):1440–1446
Ewart SL, Kuperman D et al (2000) Quantitative trait loci controlling allergen-induced airway hyperresponsiveness in inbred mice. Am J Respir Cell Mol Biol 23(4):537–545
Li Q, Verma IM (2002) NF-kappaB regulation in the immune system. Nat Rev Immunol 2(10):725–734
Mao X, Kawai QM et al (2000) Imbalance production between interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1Ra) in bronchial asthma. Biochem Biophys Res Commun 276(2):607–612
Nakae S, Komiyama Y et al (2003) IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response. Int Immunol 15(4):83-90
Nicklin MJ, Barton JL et al (2002) A sequence-based map of the nine genes of the human interleukin-1 cluster. Genomics 79(5):718-725
Park JW, Taube C et al (2004) Interleukin-1 receptor antagonist attenuates airway hyperresponsiveness following exposure to ozone. Am J Respir Cell Mol Biol 30(6):830-836
Towne JE, Garka KE et al (2004) Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs. J Biol Chem 279(14):13677-13688
Vos JB, van Sterkenburg MA et al (2005) Transcriptional response of bronchial epithelial cells to Pseudomonas aeruginosa: identification of early mediators of host defense. Physiol Genomics 21(3):324-336
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Ramadas, R.A., Li, X., Shubitowski, D.M. et al. IL-1 Receptor antagonist as a positional candidate gene in a murine model of allergic asthma. Immunogenetics 58, 851–855 (2006). https://doi.org/10.1007/s00251-006-0146-x
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DOI: https://doi.org/10.1007/s00251-006-0146-x