163. Macrophages up-regulate IL-1 receptor type 2 (IL-1R2) gene expression during acute hypoxia

IL-1R2 is a critical regulator of IL-1 bioaction but its role in acute hypoxia is not clear. Here we examine its expression during acute hypoxia. Male mice were exposed to a 6% O2 environment for 2 h. Gene transcripts for 28 inflammation-associated bioactives were examined in brain, liver, spleen, fat, and lung, and the transcript with the greatest fold elevation in all tissues was IL-1R2. In order to determine the likely cell of origin, we isolated macrophages and endothelial cells from lung because these two cell types were common to all of the aforementioned tissues. Lung macrophages from hypoxic mice expressed 104- and 163-fold more IL-1R2 than lung endothelial cells or lung tissue where the macrophages and endothelial cells had been removed. Importantly, hypoxic lung macrophages expressed four-fold more IL-1R2 than normoxic lung macrophages. Lung macrophages exposed to hypoxia ex-vivo did not up-regulate IL-1R2. Lung macrophages transferred to the peritoneum demonstrated a 225-fold increase in IL-1R2. These findings indicate the hypoxia-dependent up-regulation of IL-1R2 occurs in macrophages and is reliant on signals derived from the in vivo microenvironment.