[MRP8, MRP14 and MRP8/14 promote phenotypic maturation of mouse bone marrow-derived dendritic cells in vitro].

Objective To investigate the effects of myeloid-related protein 8 (MRP8), MRP14 and MRP8/14 heterodimer on the phenotypic maturation of mice bone marrow-derived dendritic cells (BMDCs). Methods BMDCs were cultured and purified in vitro and divided into control group (equal volume of PBS), MRP14 (1 µg/mL) treatment group, MRP8 (1 µg/mL) treatment group and MRP8/14 (1 µg/mL) treatment group. Flow cytometry was used to detect the expression of costimulatory molecules, such as CD40, CD80, CD86 and major histocompatibility complex II (MHC II ) on the surface of BMDCs after stimulation. Results MRP14, MRP8 and MRP8/14 promoted the expression of CD40, CD80 and CD86, while MRP14 and MRP8 promoted the expression of MHC II on the surface of BMDCs. Moreover, the ability to promote the expression of CD80 and CD86 is stronger in MRP14 and MRP8/14 than MRP8. Conclusion MRP14, MRP8 and MRP8/14 promote the phenotypic maturation of BMDCs by increasing the expression of costimulatory molecules, and MRP14, MRP8 and MRP8/14 also differ in their ability to promote BMDCs to expresse various costimulatory molecules.

Necrostatin-1 enhances the resolution of inflammation by specifically inducing neutrophil apoptosis.

Neutrophils play a central role in innate immunity and are rapidly recruited to sites of infection and injury. Neutrophil apoptosis is essential for the successful resolution of inflammation. Necrostatin-1 (Nec-1,methyl-thiohydantoin-tryptophan (MTH-Trp)), is a potent and specific inhibitor of necroptosis[1] (a newly identified type of cell death representing a form of programmed necrosis or regulated non apoptotic cell death) by inhibiting the receptor interacting protein 1(RIP1) kinase. Here we report that Nec-1 specifically induces caspase-dependent neutrophils apoptosis and overrides powerful anti-apoptosis signaling from survival factors such as GM-CSF and LPS. We showed that Nec-1 markedly enhanced the resolution of established neutrophil-dependent inflammation in LPS-induced acute lung injury in mice. We also provided evidence that Nec-1 promoted apoptosis by reducing the expression of the anti-apoptotic protein Mcl-1 and increasing the expression of pro-apoptotic protein Bax. Thus, Nec-1 is not only an inhibitor of necroptosis, but also a promoter of apoptosis, of neutrophils, enhancing the resolution of established inflammation by inducing apoptosis of inflammatory cells. Our results suggest that Nec-1 may have potential roles for the treatment of diseases with increased or persistent inflammatory responses.