白介素33促进低转移肺癌细胞在缺营养环境下胀亡.pptxVIP

Interleukin-33 enhances programmed oncosis of ST2L-positive low-metastatic cells in the tumour microenvironment of lung cancer;胀亡( oncosis);Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is a natural ligand for the IL-33 receptor, which is a heterodimer composed of ST2L and the IL-1 receptor accessory protein (IL-1RAcP).1–3 IL-33 is primarily expressed in epithelial cells and endothelial cells as a proinflammatory cytokine.;ST2L is expressed on the cell surface of Th2 cells, but not of Th1 cells,and on the cell surface of other immune-related cells including NK and NKT cells;ST2 and IL-33 expression in human lung cancers and pulmonary alveolar cells;ST2 mRNA was found to be significantly downregulated in lung cancers irrespective of histological types;IL-33 was detected in the nuclei of HPAEpiCs , indicating its role as an alarmin in these cells.;Among 10 cell lines, only PC-14 adenocarcinoma cells expressed a substantial amount of ST2L mRNA. However, these cells did not express IL-1RAcP mRNA;low-metastatic cells (P29and P34) derived from 3LL expressed ST2L, whereas the high-metastatic cells (D6 and A11) only slightly expressedST2L . P29 and P34 cells also expressed IL-1RAcP and MyD88;IL-33-presenting cells in 3LL tumours;The IL-33 immunofluorescence was stronger, and the number of the IL-33+ cells per mm2 was larger in P29 tumours in B6 mice than those in IL-33? /?mice;IL-1β potently induced IL-33 mRNA expression in P29 cells in a time- and dose-dependent manner None of the cytokines induced IL-33 expression in A11 cells;rIL-33 enhances the death of the low-metastatic 3LL cells under nutrient-depleted and hypoxic/anoxic conditions;rIL-33 enhanced the death of P29 and P34 cells, but not of D6 and A11 cells, in low-glucose (0.1 g/l glucose) medium (GlucL) in a dose- and time-dependent manner;These ST2L knockdown cells were refractory to rIL-33-induced cell death in GlucL medium;These results indicate that IL-33 augments the death of P29 cells via ST2L