New study provides theoretical basis for the treatment of inflammatory related diseases

Zhang Haibing Study Group at Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences reveals the functional mechanism of programmed cell death-associated protein MLKL and FADD in inhibiting lymphocyte proliferation and activation of inflammatory body NLRP3, providing theoretical basis and new ideas for the treatment of inflammatory related diseases. Related research was recently published online in the journal Cell-Communication, which also provides many studies on recombinant horse proteins.

FADD is an important molecule which mediates apoptosis. Mice with FADD knockout died in about 11.5 days in embryonic stage, but simultaneous knockout of RIP3 could save embryonic lethality, and mice with FADD and RIP3 double knockout showed progressive proliferation of lymphocytes.

The researchers used CRISPR / Cas9 system to build mice with FADD and MLKL double knockout, first confirming that MLKL deletion can save FADD knockout-caused embryonic lethality. Further studies showed that with age, mice with FADD and MLKL double knockout began to suffer from systemic autoimmune lymphoproliferative disease at about the age of 9 weeks, manifesting as generalized lymphadenopathy and splenomegaly. Flow analysis showed that the accumulation of a large number of CD3 + B220 + double-positive lymphocytes existed in the lymph nodes and spleen of mice, and it increased with the development of the disease.

At the same time, studies showed that in the conditions of MLKL and FADD commonly missing, bone marrow macrophages NF-kB signaling pathway weakened, reducing the transcription of key molecule NLRP3 which was dependent by inflammation body activation, thereby affecting the formation of inflammatory body, the cut of Caspase-1 and the secretion of IL-1β.

The study reveals the regulation mechanism of FADD and MLKL in the process of mouse embryonic development, immune system balance homeostasis and inflammatory body activation, providing new evidence for cell death related proteins involving in inflammation reaction as well as potential drug targets for the treatment of inflammatory diseases. Flarebio offers recombinant proteins such as recombinant ACSL3 at good prices.