Constitutive and LPS-regulated expression of interleukin-18 receptor beta variants in the mouse brain

Interleukin (IL)-18 is a pro-inflammatory cytokine that is proposed to be involved in physiological as well as pathological conditions in the adult brain. IL-18 acts through a heterodimer receptor comprised of a subunit alpha (IL-18R alpha) required for binding, and a subunit beta (IL-18R beta) necessary for activation of signal transduction. We recently demonstrated that the canonical alpha binding chain, and its putative decoy isoform, are expressed in the mouse central nervous system (CNS) suggesting that IL-18 may act on the brain by directly binding its receptor. Considering that the co-expression of the beta chain seems to be required to generate a functional receptor and, a short variant of this chain has been described in rat and human brain, in this study we have extended our investigation to IL-18R beta in mouse. Using a multi-methodological approach we found that: (1) a short splice variant of IL-18R beta was expressed in the CNS even if at lower levels compared to the full-length IL-18R beta variants, (2) the canonical IL-18R beta is expressed in the CNS particularly in areas and nuclei belonging to the limbic system as previously observed for IL-18R alpha and finally (3) we have also demonstrated that both IL-18R beta isoforms are up-regulated in different brain areas three hours after a single lipopolysaccharide (LPS) injection suggesting that IL-18R beta in the CNS might be involved in mediating the endocrine and behavioral effects of LPS. Our data highlight the considerable complexity of the IL-18 regulation activity in the mouse brain and further support an important central role for IL-18. (C) 2010 Elsevier Inc. All rights reserved.