The Role Of Necroptosis Signal Pathway In Intestinal Inflammation Of Adults Crohn’s Diease

BackgroundThe etiology of Crohn’s Disease (CD) remains unknown. Indeed, recent discoveries in the new caspase-independent mode of programmed cell death termed necroptosis have shed a new light in CD. Notedly, necroptosis have been found active in children with CD and contributes in intestinal inflammation. RIP3 is the core protein in necroptosis pathway, and TRAF2 is a necroptosis suppressor. We aim to study TNF-a induced necroptosis signal pathway in adult CD.MethodsBiopsy samples were randomly taken from the intestinal mucosa of 20 adult CD patients and 10 healthy controls. CD patients were allocated in two groups according to their disease phenotype (the penetrating and the stricturing). TRAF2, caspase-8, RIP3, MLKL and p-MLKL protein levels were evaluated by Western Blotting. The serous TNF-a levels were quantified by ELISA.ResultsKey proteins of necroptosis pathway such as RIP3, MLKL and p-MLKL in intestinal mucosa of CD patients were higher than those of controls. On the contraty, TRAF-2 and caspase-8 expressions were lower than controls. The serous TNF-a levels were increased in CD patients compared with those of the controls (P<0.01), with levels in penetrating group even higher than those in the structuring group. Multi-factor correlation analysis showed that serous TNF-a level was positively correlated with the protein level of RIP3(R2= 0.568, P< 0.01).The protein level of MLKL was positively correlated with p-MLKL(R2= 0.95, P< 0.0001)ConclusionsFor the first time, our results suggest that TNF-a may activate necroptosis pathway, which is associated with intestinal inflammation in adults with CD.