Abstract
Urinary tract infections (UTI) are recognized as one of the most common infectious diseases worldwide, and uropathogenic Escherichia coli (UPEC) is the main causative agent of UTI. Dendrobium officinale polysaccharides (DOPs), the main effective ingredient in Dendrobium officinale, have been reported to possess an anti-inflammatory role. Whether DOPs can attenuate the inflammatory injury (pyroptosis) induced by UPEC remains unknown. The present study aimed to assess the protective effect and potential mechanism of DOPs in UPEC-induced pyroptosis. Cell viability of THP-1 differentiated macrophage cells with DOPs was determined using MTT assay. Pyroptosis by UPEC in macrophage cells with or not DOPs pre-treatment was evaluated with flow cytometry analysis, lactate dehydrogenase (LDH) assay, and proinflammatory cytokines secretion. Expression level of key proteins in the NLRP3/Caspase-1/GSDMD pyroptotic pathway was analyzed with western blot. Furthermore the effect of DOPs on ROS activation was investigated. Results indicated that DOPs attenuated UPEC-induced cell damage in macrophage cells, inhibited the activation of NLRP3 mediated inflammasome, subsequently decreased induction and activation of caspase-1/GSDMD, and reduced the secretion of pro-inflammatory cytokine (IL-1β et al.). Moreover, pretreatment with DOPs significantly reduces ROS production, an important/putative pyroptosis stimulus signal. These results suggested that DOPs successfully mitigate UPEC-promoted pyroptosis in macrophage cells. The protective effects of DOPs are associated with the inhibition of the NLRP3/Caspase-1/GSDMD pathway and ROS signal activation.