Human FADD ELISA Matched Antibody Pair

Activation-induced cell death (AICD) mediated by the Fas/Fas ligand (FasL) system plays a key role in regulating immune response. Although normal natural killer (NK) cells use this system for their homeostasis, malignant NK cells seem to disrupt the process. Extranodal NK/T-cell lymphoma, nasal type (ENKL) is a rare but fatal disease, for which novel therapeutic targets need to be identified. We confirmed that ENKL-derived NK cell lines NK-YS and Hank1, and primary lymphoma cells expressed procaspase-8/FADD-like interleukin-1 beta-converting enzyme (FLICE) modulator and cellular FLICE-inhibitory protein (c-FLIP), along with Fas and FasL. Compared with Fas-sensitive Jurkat cells, NK-YS and Hank1 showed resistance to Fas-mediated apoptosis in spite of the same expression levels of c-FLIP and the death-inducing signaling complex (DISC) formation. Unexpectedly, the long isoform of c-FLIP (c-FLIPL) was coimmunoprecipitated with Fas predominantly in both ENKL-derived NK cell lines after Fas ligation. Indeed, c-FLIPL was more sufficiently recruited to the DISC in both ENKL-derived NK cell lines than in Jurkat cells after Fas ligation. Knockdown of c-FLIPL per se enhanced autonomous cell death and restored the sensitivity to Fas in both NK-YS and Hank1 cells. Although ENKL cells are primed for AICD, they constitutively express and efficiently utilize c-FLIPL, which prevents their Fas-mediated apoptosis. Our results show that c-FLIPL could be a promising therapeutic target against ENKL.

Aim: To investigate the protective effect of hypothermia (HT) on brain injury in moderate traumatic brain injury (TB) rat models and the potential mechanisms, especially the involvement of RIPK1 in apoptosis and necroptosis. Methods: Adult Sprague-Dawley rats were randomized to four groups: sham+normothermia (sham+NT), sham+hypothermia (sham+HT), moderate TBI+normothermia (TBI+NT) and moderate TBI+hypotherMia.(TBI+HT). The sham+HT and TBI+HT groups were submitted to 32 degrees C for 6 hours. The regional cerebral blood flow (rCBF) was assessed 24 hours after TBI; 24 and 48 hours after TBI, the modified neurological severity score (mNSS), was assessed. Immediately after behavioural tests, rats were sacrificed to harvest the brain tissues. Results: mNSS scores were lower in the IBI+HT group compared with the TBI+NT group (p < 0.01) and cerebral, blood flow was better (p < 0.01). H&E staining of the cortex and ipsilateral hippocampus showed pyknotic and irregularly shaped neuron in TBI+NT rats, which were less frequent in TBI+HT rats. The TBI+NT and TBI+HT groups showed higher TNF-alpha, TRAIL, FasL, FADD, caspase-3, caspase-8, PARP-1, RIPK-1 and RIPK-3 levels than the sham+NT group (all p < 0.05), but the levels of these proteins were all lower in the TBI+HT group compared with the TBI+NT group (all p < 0.01). Conclusion: HT treatment significantly reduced RIPK-1 upregulation, which, may inhibit necroptosis and apoptosis pathways after moderate TBI.