Da Hye Kim1,2, Soochan Kim1,2, Jin Ha Lee1,3, Jae Hyeon Kim1,4,2, Xiumei Che1,4,2, Hyun Woo Ma1,4,2, Dong Hyuk Seo1,4,2, Tae Ii Kim1, Won Ho Kim1, Seung Won Kim1,4,2, Jae Hee Cheon1,4,2. 1. Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. 2. Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. 3. Department of Health Promotion, Severance Hospital, Seoul, Korea. 4. Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Abstract
BACKGROUND AND AIM: Nuclear factor kappa B (NF-κB) activation and endoplasmic reticulum (ER) stress signaling play significant roles in the pathogenesis of inflammatory bowel disease (IBD). Thus, we evaluated whether new therapeutic probiotics have anti-colitic effects, and we investigated their mechanisms related to NF-κB and ER-stress pathways. METHODS: Luciferase, nitric oxide, and cytokine assays using HT-29 or RAW264.7 cells were conducted. Mouse colitis was induced using dextran sulfate sodium and confirmed by disease activity index and histology. Macrophages and T-cell subsets in isolated peritoneal cavity cells and splenocytes were analyzed by flow cytometry. Gene and cytokine expression profiles were determined using reverse-transcription polymerase chain reaction. RESULTS: Lactobacillus acidophilus (LA1) and Pediococcus pentosaceus inhibited nitric oxide production in RAW264.7 cells, but only LA1 inhibited Tnfa and induced Il10 expression. LA1 increased the lifespan of dextran sulfate sodium-treated mice and attenuated the severity of colitis by inducing M2 macrophages in peritoneal cavity cells and Th2 and Treg cells in splenocytes. The restoration of goblet cells in the colon was accompanied by the induction of Il10 expression and the suppression of pro-inflammatory cytokines. Additionally, we found that LA1 exerts an anti-colitic effect by improving ER stress in HT-29 cells as well as in vivo. CONCLUSIONS: We showed that LA1 significantly interferes with ER stress and suppresses NF-κB activation. Our findings suggest that LA1 can be used as a potent immunomodulator in IBD treatment, and the regulation of ER stress may have significant implications in treating IBD.
BACKGROUND AND AIM: Nuclear factor kappa B (NF-κB) activation and endoplasmic reticulum (ER) stress signaling play significant roles in the pathogenesis of inflammatory bowel disease (IBD). Thus, we evaluated whether new therapeutic probiotics have anti-colitic effects, and we investigated their mechanisms related to NF-κB and ER-stress pathways. METHODS: Luciferase, nitric oxide, and cytokine assays using HT-29 or RAW264.7 cells were conducted. Mousecolitis was induced using dextran sulfate sodium and confirmed by disease activity index and histology. Macrophages and T-cell subsets in isolated peritoneal cavity cells and splenocytes were analyzed by flow cytometry. Gene and cytokine expression profiles were determined using reverse-transcription polymerase chain reaction. RESULTS:Lactobacillus acidophilus (LA1) and Pediococcus pentosaceus inhibited nitric oxide production in RAW264.7 cells, but only LA1 inhibited Tnfa and induced Il10 expression. LA1 increased the lifespan of dextran sulfate sodium-treated mice and attenuated the severity of colitis by inducing M2 macrophages in peritoneal cavity cells and Th2 and Treg cells in splenocytes. The restoration of goblet cells in the colon was accompanied by the induction of Il10 expression and the suppression of pro-inflammatory cytokines. Additionally, we found that LA1 exerts an anti-colitic effect by improving ER stress in HT-29 cells as well as in vivo. CONCLUSIONS: We showed that LA1 significantly interferes with ER stress and suppresses NF-κB activation. Our findings suggest that LA1 can be used as a potent immunomodulator in IBD treatment, and the regulation of ER stress may have significant implications in treating IBD.
Authors: Sarah Kim; Sora Choi; Moumita Dutta; Jeffrey O Asubonteng; Marianne Polunas; Michael Goedken; Frank J Gonzalez; Julia Yue Cui; Maxwell A Gyamfi Journal: Biochem Pharmacol Date: 2021-07-23 Impact factor: 6.100
Authors: Hamid A Bakshi; Gerry A Quinn; Alaa A A Aljabali; Faruck L Hakkim; Rabia Farzand; Mohamed M Nasef; Naji Abuglela; Prawej Ansari; Vijay Mishra; Ángel Serrano-Aroca; Murtaza M Tambuwala Journal: Pharmaceuticals (Basel) Date: 2021-11-23