Necroptosis suppresses inflammation via termination of TNF- or LPS-induced cytokine and chemokine production.

TNF promotes a regulated form of necrosis, called necroptosis, upon inhibition of caspase activity in cells expressing RIPK3. Because necrosis is generally more pro-inflammatory than apoptosis, it is widely presumed that TNF-induced necroptosis may be detrimental in vivo due to excessive inflammation. However, because TNF is intrinsically highly pro-inflammatory, due to its ability to trigger the production of multiple cytokines and chemokines, rapid cell death via necroptosis may blunt rather than enhance TNF-induced inflammation. Here we show that TNF-induced necroptosis potently suppressed the production of multiple TNF-induced pro-inflammatory factors due to RIPK3-dependent cell death. Similarly, necroptosis also suppressed LPS-induced pro-inflammatory cytokine production. Consistent with these observations, supernatants from TNF-stimulated cells were more pro-inflammatory than those from TNF-induced necroptotic cells in vivo. Thus necroptosis attenuates TNF- and LPS-driven inflammation, which may benefit intracellular pathogens that evoke this mode of cell death by suppressing host immune responses.

New Jersey Caucasian, African American, and Hispanic population data on the PCR-based loci HLA-DQA1, LDLR, GYPA, HBGG, D7S8, and Gc.

New Jersey Caucasian, African American, and Hispanic genotype and allele frequencies were determined for the six PCR-based loci, HLA-DQA1, LDLR, GYPA, HBGG, D7S8, and Gc. All but one locus (HLA-DQA1 for African Americans) meet Hardy-Weinberg expectations. However, observing one departure in 18 loci over the three New Jersey sample populations is not unexpected. There is little evidence for departures from independence between pairs of loci in the three populations studied. Thus, multiple locus profile frequencies can be determined using the product rule.