Published online Aug 21, 2017. doi: 10.3748/wjg.v23.i31.5700
Peer-review started: February 22, 2017
First decision: March 3, 2017
Revised: March 30, 2017
Accepted: April 21, 2017
Article in press: April 21, 2017
Published online: August 21, 2017
Processing time: 184 Days and 7.4 Hours
To elucidate the impact of Schistosoma (S.) japonicum infection on inflammatory bowel disease by studying the effects of exposure to S. japonicum cercariae on dextran sodium sulfate (DSS)-induced colitis.
Infection was percutaneously established with 20 ± 2 cercariae of S. japonicum, and colitis was induced by administration of 3% DSS at 4 wk post infection. Weight change, colon length, histological score (HS) and disease activity index (DAI) were evaluated. Inflammatory cytokines, such as IL-2, IL-10 and IFN-γ, were tested by a cytometric bead array and real-time quantitative polymerase chain reaction (RT-PCR). Protein and mRNA levels of IRE1α, IRE1β, GRP78, CHOP, P65, P-P65, P-IκBα and IκBα in colon tissues were examined by Western blot and RT-PCR, respectively. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling positive cells, cleaved-caspase 3 expression and Bcl2/Bax were investigated to assess the apoptosis in colon tissues.
Mice infected with S. japonicum cercariae were less susceptible to DSS. Mice infected with S. japonicum cercariae and treated with DSS showed decreased weight loss, longer colon, and lower HS and DAI compared with mice treated with DSS alone. A substantial decrease in Th1/Th2/Th17 response was observed after infection with S. japonicum. Endoplasmic reticulum (ER) stress and the nuclear factor-kappa B (NF-κB) pathway were reduced in mice infected with S. japonicum cercariae and treated with DSS, along with ameliorated celluar apoptosis, in contrast to mice treated with DSS alone.
Exposure to S. japonicum attenuated inflammatory response in a DSS-induced colitis model. In addition to the Th1/Th2/Th17 pathway and NF-κB pathway, ER stress was shown to be involved in mitigating inflammation and decreasing apoptosis. Thus, ER stress is a new aspect in elucidating the relationship between helminth infection and inflammatory bowel disease (IBD), which may offer new therapeutic methods for IBD.
Core tip:Schistosoma (S.) japonicum has been demonstrated to participate in the development of colitis in animal experiments as well as clinical trials. However, the effects of Schistosoma infection on colitis and the underlying mechanism are still elusive. Here, we studied the effects of exposure to S. japonicum cercariae on dextran sodium sulfate (DSS)-induced colitis. We found that S. japonicum attenuated DSS-induced colitis in mice by reducing inflammatory response and apoptosis in colon tissues. Besides Th1/Th2/Th17 pathway and nuclear factor-kappa B pathway, endoplasmic reticulum stress played an important role in the preventive effects of parasite infection on DSS-induced colitis.