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PrP plays critical roles in modulating inflammatory responses
2017-09-21 | A A A  [print][close]

Prion protein (PrP) is up-regulated in many cell types upon cellular activation or viral infection. However, the physiological consequences of PrP up-regulation remain incompletely understood.

In a present study, the research group led by Prof. LI Chaoyang from Wuhan Institute of Virology of the Chinese Academy of Sciences found that when M2 cells were stimulated with TNFα, the TNFR signaling cascade was activated, leading to NF-κB activation and TNFα production. TNFα up-regulates the expression of pIKKα/ß, p-p65 and p-JNK, but reduces the level of IκBα. The scientists provide complementary evidence indicating that PrP is an integrate component of this signaling pathway. When PRNP is deleted in M2 cells, these signaling events are greatly reduced.

Most importantly, re-introduction of PRNP into PrP null M2 cells restores p-p65 signaling cascade, albeit not as robust as observed in the wildtype M2 cells. Similar results were observed in a PDAC cell line, BxPC-3. When PrP is eliminated from BxPC-3, it also greatly reduced NF-κB activation upon TNFαtreatment.

Therefore, their observation that PrP is important in TNFα signaling is not limited to M2. Expression of PrP also appears to be important in regulating IL-6 production.

In conclusion, the scientists found that PrP enhances the responses to TNFα, promoting

proinflammatory cytokine production, which may contribute to inflammation and tumorigenesis.

The results have been published in Journal of Biological Chemistry entitled "Prion protein is required for tumor necrosis factor alpha (TNFα)-triggered nuclear factor kappa B (NF-κB) signaling and cytokine production".

This work was supported by grants from Strategic Priority Research Program A of the Chinese Academy of Sciences, National Science Foundation of China, Nature Science Foundation of Hubei Province and National Basic Research Priorities Program of China.

 

Contact:

LI Chaoyang

Email: cyli@wh.iov.cn

Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China (http://english.whiov.cas.cn/) 

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