Celastrol inhibits pro-inflammatory cytokine secretion in Crohn’s disease biopsies

Crohns disease is a chronic intestinal inflammatory process. In modern therapy, TNF-a inhibition is the main goal. The aim here is to characterize the effects of Celastrol, a pentacyclic-triterpene, on the secretion of inflammatory cytokines by LPS-activated human cells. Celastrol dose-dependently inhibited the secretion of all tested pro-inflammatory cytokines with IC50 in the nanomolar range. Effect not related to glucocorticoid receptor activity is shown by competition experiments with the steroid antagonist RU486. Celastrol inhibited the pro-inflammatory cytokine secretion from mucosal inflammatory biopsies from Crohns disease patients. Cytometry emphasized that for all tested pro-inflammatory cytokines, CD33 + cells are the most sensitive. Quantitative-PCR and confocal analysis on a human monocytic cell line indicated that Celastrol acts at the transcriptional level by inhibiting LPS-induced NF-jB translocation. Celastrol might be a putative anti-inflammatory drug in the treatment of inflammatory diseases, given its inhibition of cytokine production by intestinal biopsies from Crohns disease patients.