Cell Death Dis
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Group 2 innate lymphoid cells (ILC2) are one of three subgroups of innate lymphoid cells (ILC1, ILC2, and ILC3), and the major ILC population detected in the lungs. The function of ILC2 in the regulation of lung inflammation remains unclear. ⋯ We further showed that the increased ILC2 in the lungs secrete IL-9, which in turn prevents lung EC from undergoing pyroptosis, a pro-inflammatory cell death form, by attenuating caspase-1 activation. These findings suggest a previously unidentified innate pathway that negatively regulates lung inflammation following sepsis.
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Recent studies have shown that after traumatic brain injury (TBI), the number of autophagosomes is markedly increased in brain cells surrounding the wound; however, whether autophagy is enhanced or suppressed by TBI remains controversial. In our study, we used a controlled cortical impact system to establish models of mild, moderate and severe TBI. In the mild TBI model, the levels of autophagy-related protein 6 (Beclin1) and autophagy-related protein 12 (ATG12)-autophagy-related protein 5 (ATG5) conjugates were increased, indicating the enhanced initiation of autophagy. ⋯ Thus, A2AR may be involved in regulating the impairment of autophagic flux in response to brain injury. Our findings suggest that whether autophagy is increased after TBI is associated with whether autophagic flux is impaired, and the impairment of autophagic flux exacerbates the severity of trauma. Furthermore, A2AR may be a target for alleviating the impairment in autophagic flux after TBI.
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Cigarette smoking is a major risk factor for atherosclerosis and other cardiovascular diseases. Increasing evidence has demonstrated that nicotine impairs the cardiovascular system by targeting vascular endothelial cells, but the underlying mechanisms remain obscure. It is known that cell death and inflammation are crucial processes leading to atherosclerosis. ⋯ Moreover, silencing NLRP3 or ASC by small interfering RNA efficiently suppressed nicotine-induced caspase-1 cleavage, IL-18 and IL-1β production, and pyroptosis in HAECs. Further experiments revealed that the nicotine-NLRP3-ASC-pyroptosis pathway was activated by reactive oxygen species (ROS), since ROS scavenger (N-acetyl-cysteine, NAC) prevented endothelial cell pyroptosis. We conclude that pyroptosis is likely a cellular mechanism for the pro-atherosclerotic property of nicotine and stimulation of ROS to activate NLRP3 inflammasome is a signaling mechanism for nicotine-induced pyroptosis.
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Annexin A3 (ANXA3) is dysregulated and plays an important role in various cancers. However, the role of ANXA3 in breast cancer is still unclear. Here, we observed that the expression level of ANXA3 was significantly upregulated in breast cancer tissues. ⋯ In addition, we demonstrated that ANXA3 knockdown increased the sensitivity of breast cancer cells to doxorubicin by increasing the drug uptake. The combination of ANXA3 knockdown and doxorubicin treatment simultaneously inhibited tumor growth and metastasis in vivo. This study described the role and mechanisms of ANXA3 in regulating BCSCs and breast cancer growth and metastasis, indicating that downregulating ANXA3 together with chemotherapy might be a novel therapeutic strategy for treating breast cancer.
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To examine the temporal relationship of cortical autophagic flux with delayed neuronal cell death after hypoxia-ischemia (HI) in neonatal piglets. HI was produced with 45-min hypoxia and 7-min airway occlusion in 3-5-day-old piglets. Markers of autophagic, lysosomal and cell death signaling were studied via immunohistochemistry, immunoblotting, and histochemistry in piglet brains. ⋯ Beclin-1 colocalized with markers of caspase-dependent and caspase-independent apoptosis and necrosis in neurons. In vitro, mouse neonatal cortical neurons treated with rapamycin and chloroquine showed increased autophagosomes, but not autolysosomes, and increased cell death that was attenuated by cyclosporine A. Neonatal HI initially increases autophagy but later impairs autophagosome clearance, coinciding with delayed cortical neuronal death.