1. PYR-41 and Thalidomide Impair Dendritic Cell Cross-Presentation by Inhibiting Myddosome Formation and Attenuating the Endosomal Recruitments of p97 and Sec61 via NF- B Inactivation.
- Author
-
You, Xiang, Xu, Dan Dan, Zhang, Di, Chen, Jie, and Gao, Feng Guang
- Subjects
- *
THALIDOMIDE , *INFLAMMATION treatment , *DRUG side effects , *NEOPLASTIC cell transformation , *PHTHALIMIDES , *THERAPEUTICS , *PROTEIN metabolism , *ANIMAL experimentation , *ANTI-infective agents , *CELLULAR immunity , *CELLULAR signal transduction , *CYTOPLASM , *DENDRITIC cells , *HETEROCYCLIC compounds , *IMMUNOSUPPRESSIVE agents , *MICE , *PROTEINS , *DNA-binding proteins , *NUCLEAR proteins - Abstract
PYR-41 and thalidomide have therapeutic effects on inflammation-associated diseases with side effects such as tumorigenesis. Cross-presentation allows dendritic cells (DC) to present endogenous antigen and induce protective immunity against microbe infection and tumors. But, up to now, the effects of PYR-41 and thalidomide on cross-presentation are still uncertain. In this study, we investigated the effect and mechanism of PYR-41 and thalidomide on DC cross-presentation by observing Myddosome formation, endosomal recruitment of p97 and Sec61, NF-κB activation, and cross-priming ability. We demonstrated that the inhibition of endosomal recruitment of p97 and Sec61, together with attenuated NF-κB activation and Myddosome formation, contributes to PYR-41- and thalidomide-impaired cross-presentation and thereby reverses cross-activation of T cells. These observations suggest that NF-κB signaling and p97 and Sec61 molecules are candidates for dealing with the side effects of PYR-41 and thalidomide. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF