The involvement of mast cells in the irinotecan-induced enteric neurons loss and reactive gliosis

Background: the irinotecan (cpt-11) causes intestinal mucositis and diarrhea that may be related to changes in the enteric nervous system (ens). in inflammatory condition,mast cells release a variety of pro-inflammatory mediators that can interact with the ens cells. it has not been explored whether cpt-11 is able to alter the enteric glial and neuronal cell,and the role of mast cells in this effect. therefore,this study was conducted to investigate the effect of cpt-11 on the enteric glial and neuronal cells,as well as to study the role of mast cells in the cpt-11-induced intestinal mucositis. methods: intestinal mucositis was induced in swiss mice by the injection of cpt-11 (60mg/kg,i.p.) once a day for 4days following by euthanasia on the fifth day. to investigate the role of mast cells,the mice were pretreated with compound 48/80 for 4days (first day,0.6mg/kg; second day,1.0mg/kg; third day,1.2mg/kg; fourth day,2.4mg/kg) to induce mast cell degranulation before the cpt-11 treatment. results: here,we show that cpt-11 increased glial fibrillary acidic protein (gfap) and s100β gene and s100β protein expressions and decreased huc/d protein expression in the small intestine segments. concomitantly,cpt-11 enhanced tumor necrosis factor-α (tnf-α) and interleukin-6 (il-6) levels and inducible nitric oxide synthase (inos) gene expression,associated with an increase in the total number macrophages (positive cells for ionized calcium-binding adapter molecule,iba-1) and degranulated mast cells in the small intestine segments and caused significant weight loss. the pretreatment with compound 48/80,an inductor of mast cells degranulation,significantly prevented these cpt-11-induced effects. conclusions: our data suggests the participation of mast cells on the cpt-11-induced intestinal mucositis,macrophages activation,enteric reactive gliosis,and neuron loss. © 2017 the author(s).