胸腔积液 IL-33/sST2 水平及低和高 IL-33/sST2 水平对人胸膜细胞黏附和迁移的影响。

Pleural Effusion IL-33/sST2 Levels and Effects of Low and High IL-33/sST2 Levels on Human Mesothelial Cell Adhesion and Migration.

机构信息

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500, Larissa, Greece.

Department of Physiology, Faculty of Medicine, University of Thessaly, 3 Panepistimiou Str., BIOPOLIS, 41500, Larissa, Greece.

出版信息

Inflammation. 2019 Dec;42(6):2072-2085. doi: 10.1007/s10753-019-01070-6.

DOI:10.1007/s10753-019-01070-6

PMID:31429014

Abstract

Interleukin 33 (IL-33) is an alarmin with multiple roles in immunity and cell homeostasis, highly expressed in barrier sites, acting via the suppression of tumorigenicity 2 receptor (ST2). Production of IL-33 and soluble ST2 (sST2), a decoy receptor for IL-33, has been implicated in several pulmonary diseases, but both have been scarcely investigated in pleural diseases. The aim of this study was to determine the levels of IL-33 and sST2 in transudative (TrPEs), malignant (MPEs), and parapneumonic (PPEs) pleural effusions (PEs) and investigate the effect of PE fluids from each group with low and high IL-33/sST2 levels on MeT-5A cell adhesion and migration. IL-33 and sST2 pleural fluid levels were similar among TrPEs, MPEs, and PPEs. However, a significant correlation was found between IL-33 and LDH and in sST2 levels with lymphocyte counts in TrPEs. Additionally, in MPEs the levels of IL-33 correlated with the levels of sST2 and with the red blood cell counts. Furthermore, incubation of MeT-5A cells with MPEs and PPEs bearing low or high levels of IL-33/sST2 yielded significant differential effects on MeT-5A cell adhesion and migration. In MPEs, high IL-33/sST2 levels led to increased adhesion and migration of MeT-5A cells, while in PPEs the effect was the opposite, while no effect in both cell phenotypes was determined for TrPEs. These results reveal a clinical context dependent effect of the IL-33/sST2 axis in PEs.

摘要

白细胞介素 33（IL-33）是一种具有多种免疫和细胞内稳态作用的警报素，在屏障部位高表达，通过抑制肿瘤抑制物 2 受体（ST2）发挥作用。IL-33 和可溶性 ST2（sST2）的产生，IL-33 的诱饵受体，已被牵连到几种肺部疾病中，但在胸膜疾病中都很少被研究。本研究旨在确定渗出性（TrPEs）、恶性（MPEs）和类肺炎性（PPEs）胸腔积液（PEs）中 IL-33 和 sST2 的水平，并研究每组具有低和高 IL-33/sST2 水平的胸腔积液对 MeT-5A 细胞黏附和迁移的影响。TrPEs、MPEs 和 PPEs 之间 IL-33 和 sST2 胸腔液水平相似。然而，在 TrPEs 中发现 IL-33 与 LDH 之间存在显著相关性，而 sST2 水平与淋巴细胞计数之间存在相关性。此外，在 MPEs 中，IL-33 水平与 sST2 水平以及红细胞计数相关。此外，用具有低或高 IL-33/sST2 水平的 MPEs 和 PPEs 孵育 MeT-5A 细胞会对 MeT-5A 细胞黏附和迁移产生显著的差异影响。在 MPEs 中，高 IL-33/sST2 水平导致 MeT-5A 细胞的黏附和迁移增加，而在 PPEs 中则相反，而 TrPEs 对两种细胞表型均无影响。这些结果揭示了 IL-33/sST2 轴在 PEs 中具有临床相关的作用。