Saluja R, Hawro T, Eberle J, Church M K, Maurer M
Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Germany.
J Biol Regul Homeost Agents. 2014 Oct-Dec;28(4):575-85.
Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is emerging as a new modulator of immune and inflammatory responses. Although IL-33 and its associated receptor ST2 are reportedly expressed in mast cells (MCs), the precise role of IL-33 in modulating MC function has not been determined. In the present studies, we explored IL-33 effects on MCs in vivo and in vitro. IL-33 increased the number of peritoneal and skin MCs in vivo. IL-33 also resulted in increased proliferation of MCs in vitro, as explored by WST assay. Cell cycle analysis further confirmed this result by showing increased G2 cell populations in MCs stimulated with IL-33. We found that IL-33-mediated MC proliferation requires ST2 and MyD88, is independent of Kit, and is mediated through a p38 MAPK-dependent pathway. IL-33 did not induce degranulation and was not cytotoxic for MCs. This novel mechanism for increasing MC proliferation and numbers further defines the role of IL-33 in MC-dependent diseases including allergies and may help to develop novel approaches for the treatment of these disorders.
白细胞介素-33（IL-33）是白细胞介素-1细胞因子家族的成员，正逐渐成为免疫和炎症反应的新型调节因子。尽管据报道IL-33及其相关受体ST2在肥大细胞（MC）中表达，但IL-33在调节MC功能方面的确切作用尚未确定。在本研究中，我们在体内和体外探究了IL-33对MC的影响。IL-33在体内增加了腹膜和皮肤MC的数量。如通过WST检测所探究的，IL-33在体外也导致MC增殖增加。细胞周期分析通过显示在用IL-33刺激的MC中G2细胞群体增加进一步证实了这一结果。我们发现IL-33介导的MC增殖需要ST2和MyD88，不依赖于Kit，并且是通过p38丝裂原活化蛋白激酶（MAPK）依赖性途径介导的。IL-33不诱导脱颗粒，对MC也没有细胞毒性。这种增加MC增殖和数量的新机制进一步明确了IL-33在包括过敏在内的MC相关疾病中的作用，并可能有助于开发治疗这些疾病的新方法。
