IL-1 Receptor antagonist as a positional candidate gene in a murine model of allergic asthma.

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.