PDF(Pubmed)
Abstract：
Severe asthma and sinus disease are consequences of type 2 inflammation (T2I), mediated by interleukin (IL)-33 signaling through its membrane-bound receptor, ST2. Soluble (s)ST2 reduces available IL-33 and limits T2I, but little is known about its regulation. We demonstrate that prostaglandin E2 (PGE2) drives production of sST2 to limit features of lung T2I. PGE2-deficient mice display diminished sST2. In humans with severe respiratory T2I, urinary PGE2 metabolites correlate with serum sST2. In mice, PGE2 enhanced sST2 secretion by mast cells (MCs). Mice lacking MCs, ST2 expression by MCs, or E prostanoid (EP)2 receptors by MCs showed reduced sST2 lung concentrations and strong T2I. Recombinant sST2 reduced T2I in mice lacking PGE2 or ST2 expression by MCs back to control levels. PGE2 deficiency also reversed the hyperinflammatory phenotype in mice lacking ST2 expression by MCs. PGE2 thus suppresses T2I through MC-derived sST2, explaining the severe T2I observed in low PGE2 states.
摘要：
严重的哮喘和鼻窦疾病是2型炎症（T2I）的后果，由白细胞介素（IL）-33通过其膜结合受体介导，ST2.可溶性ST2降低可用IL-33并限制T2I，但对其监管知之甚少。我们证明前列腺素E2（PGE2）驱动sST2的产生以限制肺T2I的特征。PGE2缺陷型小鼠显示sST2减少。在患有严重呼吸道T2I的人类中，尿PGE2代谢产物与血清sST2相关。在老鼠身上,PGE2增强肥大细胞(MC)的sST2分泌。缺乏MC的小鼠，通过MC表达ST2，MC或E类前列腺素（EP）2受体显示sST2肺浓度降低和T2I强。重组sST2将缺乏MCs的PGE2或ST2表达的小鼠中的T2I降低至对照水平。PGE2缺乏也逆转了MCs缺乏ST2表达的小鼠的高炎性表型。因此，PGE2通过MC衍生的sST2抑制T2I，解释了在低PGE2状态下观察到的严重T2I。
