Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension

The IL-33/ST2 axis: Role in health and disease

“…Expression of an IL-33 mutant lacking the N-terminal domain needed for nuclear localization demonstrates its role in immune homeostasis in vivo, because mice heterozygous for the mutant protein exhibit poor survival, high serum IL-33 levels, and a marked inflammatory and eosinophilic infiltration into various organs [14]. Consistent with these observations, patients with idiopathic pulmonary arterial hypertension (IPAH), characterized by increased circulating levels of cytokines, have lower nuclear IL-33 content in lung endothelial cells than control subjects [13]. Together, these data suggest that nuclear full-length (IL-33 ) plays a role in homeostasis by modulating cytokine gene expression, although the mechanisms await further investigation.…”

“…IL-1b enhances the full-length IL-33 binding to the NF-kB p65 subunit in the cytosol and nucleus, thus decreasing transcription factor binding to DNA-response elements and transactivation of target genes, such as tumor necrosis factor-a (TNF-a) and IkBa [12]. Moreover, IL-33-deficient human endothelial cells show altered expression of NF-kB-dependent genes, such as IL-6, and down-regulation of the chemokines RANTES and Fractalkine [13]. Expression of an IL-33 mutant lacking the N-terminal domain needed for nuclear localization demonstrates its role in immune homeostasis in vivo, because mice heterozygous for the mutant protein exhibit poor survival, high serum IL-33 levels, and a marked inflammatory and eosinophilic infiltration into various organs [14].…”

New insights into the pathogenesis of giant cell arteritis

“…Interestingly, GCA patients with higher IL-6 levels experience more relapses and require higher doses of GC during follow-up. It has been recently demonstrated that the expression of IL-6 close depends on two different cytokines of the innate immunity, IL-32 and IL-33 signalling [64,65]. IL-32 is a recently described Th1-related pro-inflammatory cytokine with important functions in both innate and immune responses [66].…”

L’interleukine-33 : une cible thérapeutique potentielle de la néo-angiogenèse associée à l’asthme

“…Chez ces patients, la concentration sérique de la forme soluble du récepteur ST2 (sST2) est augmentée. In vitro, les cellules endothéliales ont une réduc-tion de la production de la protéine sST2 par un mécanisme qui implique la formation d'un complexe répresseur entre l'IL-33 et l'histone méthyltransférase SUV39H1 sur le promoteur ST2 [12]. Le récepteur sST2 dépourvu des domaines transmembranaire et cytoplasmique a des propriétés immunosuppressives en agissant tel un récepteur leurre pour l'IL-33, inhibant ainsi son activité de cytokine.…”