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The interferon-related developmental regulator 1 is a key factor for human papillomavirus-induced NFкB inhibition

 

High-risk human papillomaviruses (hrHPVs) primarily target undifferentiated keratinocytes (KCs) and evade host immunity despite some keratinocytes with well response of innate and adaptive immune signals. Previous studies have reported cellular deubiquitinase ubiquitin carboxy-terminal hydrolase L1 (UCHL1) may play a role in HPV infection via impairation of pattern recognition receptor (PRR)-induced NFкB activation. However, the finding cannot explain how the virus prevent the KCs from responding to adaptive immune signals. Tummers et al. found hrHPV impairs immune response by inhibiting the acetylation of NFкB/RelA K310 in keratinocytes. The article was published in Nature Communication.

 

By using freshly established or persistent hrHPV-infected keratinocytes as well as healthy keratinocytes as control, researchers observed infected keratinocytes show a decreased pro-inflammatory cytokine production and immune cell recruitment in response to innate or adaptive immune signals. Mechanically, HPV increases the expression of interferon-related developmental regulator 1 (IFRD1) during this process. In addition, EGFR signaling is involved in the IFRD1 upregulation. Cytokine expression can be increased by treatment of IFRD1 shRNA, EGFR inhibitor cetuximab or the HDAC1/3 inhibitor extimostat, result from restoration of NFкB/Rel A acetylation. The findings reveal part of mechanism of HPV immune evasion, which may be helpful for further study of clinical strategy against hrHPV.

 

Reference:
Nat Commun. 2015 Mar 13;6:6537. doi: 10.1038/ncomms7537.

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