Immunomdulatory Effects Of P53 And NF-?B Signaling Pathways In AEC? Cells Infected With MTB

Alveolar type ? epithelial cells(AEC II)play an important role in immune regulation against Mycobacterium tuberculosis(MTB)infection,but its specific regulatory mechanism has not yet been elucidated.The NF-?B signaling pathway plays an important regulatory role in the inflammatory response to pathogenic bacteria(such as MTB etc.)infecting.p53 signaling pathway is involved in the development of cancer and other infectious diseases.These studies suggest thatwhether the p53 signaling pathway and the NF-?B signaling pathway are coordinate regulation of the innate immune response to against the MTB infection in AEC II cells?In this study,a model of Bacillus Calmette-Guerin(BCG)attenuated Bacillus Calmette-Guerin(BCG)gene over expression/interference of A549 cells was established.The results were analyzed by RT-PCR,Western Blot and inflammatory factor protein quantification chip technology.The expression patterns of p53 and NF-kappaB signaling pathway related signaling molecules and inflammatory cytokines are expected to find a cross-talk relationship between p53 and NF-kappaB signaling pathways in the AEC II anti-MTB immune response process.Through experimental analysis,it was found that the effect of BCG on p53-overexpressed A549 cells promoted the expression of p53,p-MDM2,TNF-a and IL-8,and inhibited TLR-4,NF-?B,TRAF6,MDM2,CBP,IL-6 and IFN-y.The expression of p53,CBP and TRAF6 were inhibited,and the expression of MDM2/p-MDM2,NF-?B,TLR-4,TNF-?,IFN-?,IL-6 and IL-8 were up-regulated in p53-inhibited A549 cells after stimulated with BCG.BCG inhibited the expression of p53 and MDM2 in NF-?B over-expressed A549 cells and promoted NF-?B,TLR-4,TRAF6,p-MDM2,CBP,TNF-a,IFN-y,IL-6 and IL-8 expression;A549 cells interfered with NF-?B gene interference by BCG promoted the expression of NF-?,TLR-4,TRAF6,MDM2/p-MDM2,CBP and TNF-a,but the expressions of p53,IFN-y,IL-6 and IL-8 were inhibited.These results reveal that p53 signaling pathway is involved in the anti-tuberculosis immune regulation of AEC II cells by negatively regulating NF-?B signaling pathway and controlling cellular inflammatory responses.The studies have laid a theoretical basis for further research on innate immunityof the regulation of p53 and NF-?B signaling pathway in AEC ?cells against-MTB infection.