Abstract
Crohn's disease is a common, chronic inflammatory bowel condition characterized by remission and relapse. Accumulating evidence indicates that activated T cells play an important role in this disease. In the present study, we aimed to examine the effect of beauvericin, a natural cyclic peptide, on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice, which mimics Crohn's disease. Beauvericin significantly reduced weight loss, diarrhea and mortality, accompanied with notable alleviation of macroscopic and microscopic signs. In addition, this compound decreased serum levels of tumor necrosis factor (TNF)-α and interferon (IFN)- γ in a concentration-dependent manner in mice with experimental colitis. These effects of beauvericin are attributed to its inhibition on activated T cells. Flow cytometry and immunoblot assay data showed that beauvericin suppressed T-cell proliferation, activation and IFN-γ-STAT1-T-bet signaling and subsequently led to apoptosis of activated T cells by suppressing Bcl-2 and phosphorylated Bad as well as increasing cleavage of caspase-3, -9, -12 and PARP. Furthermore, inhibition of PI3K/Akt signaling, which was an upstream regulator of cell activation and survival in activated T cells, contributed to the effect of beauvericin. Overall, these results supported beauvericin as a novel drug candidate for the treatment of colonic inflammation mainly by targeting PI3K/Akt in activated T cells.
Highlights
Crohn’s disease is a chronic inflammatory bowel condition, characterized by remission and relapse, with a high incidence of 27–48 cases per 100,000 persons per year in western countries [1]
To determine the immunomodulatory activity of beauvericin, we investigated its therapeutic efficacy in TNBSinduced T cell-mediated murine colitis
The intracolonic administration of trinitrobenzene sulfonic acid (TNBS) in mice induced a severe illness that was characterized by body weight loss, stool consistency alterations, and bleeding, which peaked at day 2–3 after challenge, with mortality thereafter
Summary
Crohn’s disease is a chronic inflammatory bowel condition, characterized by remission and relapse, with a high incidence of 27–48 cases per 100,000 persons per year in western countries [1]. The mucosa of patients with established Crohn’s disease are dominated by CD4+ T lymphocytes, which are distinguished by their capacity for producing interferon-c (IFN-c) and interleukin-2 (IL-2) [3,4,5]. To mimic this disease in mice, a chemically induced model of colonic inflammation has been developed. It has been demonstrated that murine models featuring an activated PI3K/Akt/ mTOR signaling pathway in lymphocytes exhibit signs of systemic autoimmunity [13] that link this pathway to autoimmune disorders. Inhibiting PI3K/Akt signaling may prevent inflammatory bowel disease development mediated by activated T lymphocytes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
