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

ABSTRACT: 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?) required for binding, and a subunit beta (IL-18R?) 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? in mouse. Using a multi-methodological approach we found that: (1) a short splice variant of IL-18R? was expressed in the CNS even if at lower levels compared to the full-length IL-18R? variants, (2) the canonical IL-18R? is expressed in the CNS particularly in areas and nuclei belonging to the limbic system as previously observed for IL-18R? and finally (3) we have also demonstrated that both IL-18R? isoforms are up-regulated in different brain areas three hours after a single lipopolysaccharide (LPS) injection suggesting that IL-18R? 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.

SUBMITTER: Alboni S 

PROVIDER: S-EPMC6810603 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature