Functional characterisation of Holothuria leucospilota Fas-associated death domain in the innate immune-related signalling pathways

Abstract

In this study, the functions of Holothuria leucospilota Fas-associated death domain (HLFADD) in the innate immune-related signalling pathways were investigated. The results showed that over-expression of HLFADD in HEK293T cells could activate the transcription factors NF-κB and activator protein-1 (AP-1), and induce the secretion of downstream pro-inflammatory cytokines IL-6, IL-8 and IL-18, suggesting the involvement of the sea cucumber FADD in activating the NF-κB and c-Jun NH2-terminal kinase-dependent pathways. On the other hand, HLFADD could down-regulate the activations of NF-κB and AP-1 that induced by over-expression of H. leucospilota myeloid differentiation factor 88 (HLMyD88), which is supposed to be mediated through its interaction with HLMyD88 to keep the MyD88-dependent TLR signalling at a proper magnitude. The interaction of HLFADD and HLMyD88 were further supported by a co-immunoprecipitation assay. Moreover, HLFADD could activate transcription factor IFN regulatory factor-3 and induced the secretion of downstream IFN-α and IFN-β, indicating that the sea cucumber FADD may also activate the antiviral IFN signalling pathway. In summary, our study may give new insights on the functions of sea cucumber FADD in the innate immune-related signalling pathways.