Lactobacillus acidophilus suppresses intestinal inflammation by inhibiting endoplasmic reticulum stress
Da Hye Kim
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
These authors contributed equally to this work.Search for more papers by this authorSoochan Kim
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
These authors contributed equally to this work.Search for more papers by this authorJin Ha Lee
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Department of Health Promotion, Severance Hospital, Seoul, Korea
These authors contributed equally to this work.Search for more papers by this authorJae Hyeon Kim
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorXiumei Che
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorHyun Woo Ma
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorDong Hyuk Seo
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorTae II Kim
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorWon Ho Kim
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorCorresponding Author
Seung Won Kim
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
Correspondence
Dr Jae Hee Cheon, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.
Email: [email protected]
Dr Seung Won Kim, Department of Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Jae Hee Cheon
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
Correspondence
Dr Jae Hee Cheon, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.
Email: [email protected]
Dr Seung Won Kim, Department of Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.
Email: [email protected]
Search for more papers by this authorDa Hye Kim
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
These authors contributed equally to this work.Search for more papers by this authorSoochan Kim
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
These authors contributed equally to this work.Search for more papers by this authorJin Ha Lee
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Department of Health Promotion, Severance Hospital, Seoul, Korea
These authors contributed equally to this work.Search for more papers by this authorJae Hyeon Kim
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorXiumei Che
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorHyun Woo Ma
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorDong Hyuk Seo
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorTae II Kim
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorWon Ho Kim
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorCorresponding Author
Seung Won Kim
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
Correspondence
Dr Jae Hee Cheon, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.
Email: [email protected]
Dr Seung Won Kim, Department of Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Jae Hee Cheon
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
Correspondence
Dr Jae Hee Cheon, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.
Email: [email protected]
Dr Seung Won Kim, Department of Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.
Email: [email protected]
Search for more papers by this authorAbstract
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.
Supporting Information
| Filename | Description |
|---|---|
| jgh14362-sup-0001_Supplementary_Information_cleared.docWord document, 69.5 KB |
Table S1. List of primers used for qRT-PCR. |
| jgh14362-sup-0003-Supplementary_Fig-1b.tifTIFF image, 707.6 KB |
Figure S1a. Flow-cytometric analysis strategy. (a) Analysis of F4/80+CD206+ and TREM-1+ populations in peritoneal cavity cells (PCCs). (b) Analysis of CD3+CD4+GATA3+ and Foxp3+ populations in splenocytes. |
| jgh14362-supp-0002-Supplementary_Fig-1a.tifTIFF image, 698.9 KB |
Figure S1b. Flow-cytometric analysis strategy. (a) Analysis of F4/80+CD206+ and TREM-1+ populations in peritoneal cavity cells (PCCs). (b) Analysis of CD3+CD4+GATA3+ and Foxp3+ populations in splenocytes. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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