白介素33促进低转移肺癌细胞在缺营养环境下胀亡__培训课件.pptxVIP

Interleukin-33 enhances programmed oncosis of ST2L-positive low-metastatic cells in the tumour microenvironment of lung cancer胀亡( oncosis)胀亡：细胞肿胀和核溶解的细胞损伤过程胀亡的形态学特征 胀亡细胞的形态学表现为细胞肿胀,体积增大,胞浆空泡化,胞浆内出现致密颗粒,内质网肿胀,线粒体早期可出现致密化,后期肿胀,絮状改变或出现高致密颗粒,嵴破坏; 细胞肿胀波及核,核内染色质分散,凝集在核膜、核仁周围,有时聚集成团块;胞膜起泡是胀亡早期事件,随之胞膜通透性增加,胞膜崩解。 胀亡细胞后期往往表现为核溶解,由于胞内容物外溢,胀亡细胞周围有明显炎症反应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. IL-33 is usually localised in the cell nucleus as an alarmin that signals to local immune cells in response to tissue damage caused by injury,necrosis or exposure to pathogensIL-33 polarises naiveT cells to produce Th2-associated cytokines, it strongly induces proinflammatory cytokine and chemokine production by mast cells and eosinophils, and it stimulates the polarisation of alternatively activated M2 macrophagesIL-33 has an important role in Th2 immunity and Th2-related diseasesST2L 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 cellsST2 and IL-33 expression in human lung cancers and pulmonary alveolar cellsST2 mRNA was found to be significantly downregulated in lung cancers irrespective of histological typesSurvival analysis in PrognoScan database also revealed that the ST2 expression level was inversely correlated with relapsefreesurvival and overall survivalIL-33 mRNA was significantly downregulated in lung cancers, inversely correlating with the malignancy indexqRT-PCR analysis revealed that ST2L, sST2, asecreted soluble ST2 that acts as a decoy receptor for IL-33,IL-1RAcP, MyD88 and IL-33 were expressed in HPAEpiCs,whereas those genes were significantly downregulated inA549 cellsIL-33 was detected in the nuclei of HPAEpiCs , indic