RESUMO
Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.
Assuntos
Humanos , Antígeno B7-H1/metabolismo , Células-Tronco Mesenquimais/imunologia , Linfócitos T/metabolismo , ImunomodulaçãoRESUMO
Objective:To investigate the effects of capsaicin on colon cancer SW480 cells and the underlying molecular mechanism through the transient receptor potential vanilloid 1(TRPV1). Method:Capsaicin groups with different concentrations and a blank group were set up. The cell viability was detected by cell counting kit-8 (CCK-8) after SW480 cells were treated with capsaicin(50,100,200,300,400,500,600,800,1 000 μmol·L<sup>-1</sup>) for 12,24,and 48 h to select the concentration of capsaicin which can effectively inhibit proliferation. The cell cycle and apoptosis were detected by flow cytometry after SW480 cells were treated with capsaicin (200,400,800 μmol·L<sup>-1</sup>) for 24 h. The protein expression levels of TRPV1,p53,p-p53,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),cleaved cysteinyl aspartate-specific protease-3(cleaved Caspase-3),cleaved Caspase-8,and cleaved poly adenosine diphosphate ribose polymerase (PARP) were detected by Western blot after SW480 cells were treated with capsaicin (200,400 μmol·L<sup>-1</sup>) for 24 h.In addition,the apoptosis was detected after SW480 cells were treated with TRPV1 microRNA(mRNA) and capsaicin(200 μmol·L<sup>-1</sup>). Western blot analysis was used to detect the protein expression levels of the above proteins. Result:As compared with the blank group,capsaicin(≥200 μmol·L<sup>-1</sup>)significantly inhibited the cell viability of SW480 cells(<italic>P</italic><0.01) in dose- and time-dependent manners. The cell cycle was arrested in G<sub>2</sub>/M phase by 200 and 400 μmol·L<sup>-1</sup> capsaicin treatment,and arrested in G<sub>1</sub> phase by 800 μmol·L<sup>-1</sup> capsaicin treatment (<italic>P</italic><0.05). Flow cytometry showed that capsaicin (200, 400, 800 μmol·L<sup>-1</sup>) significantly promoted apoptosis of SW480 cells simultaneously(<italic>P</italic><0.05,<italic>P</italic><0.01). Western blot showed that capsaicin (200,400 μmol·L<sup>-1</sup>) significantly up-regulated the protein levels of apoptosis-related proteins(p53,p-p53,Bax,cleaved Caspase-3,cleaved Caspase-8,and cleaved PARP) (<italic>P</italic><0.05,<italic>P</italic><0.01),and significantly down-regulated Bcl-2(<italic>P</italic><0.01). In addition,siRNA-mediated knockdown of TRPV1 significantly attenuated capsaicin-induced apoptosis and the protein levels of apoptosis-related proteins in SW480 cells(<italic>P</italic><0.05,<italic>P</italic><0.01). Conclusion:Capsaicin can inhibit cell proliferation,arrest cell cycle,and induce apoptosis of SW480 cells,and the possible mechanism may be related to TRPV1 activation.