PMID- 35955675 OWN - NLM STAT- MEDLINE DCOM- 20220815 LR - 20220815 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 15 DP - 2022 Aug 1 TI - Psychological Stress Exacerbates Inflammation of the Ileum via the Corticotropin-Releasing Hormone-Mast Cell Axis in a Mouse Model of Eosinophilic Enteritis. LID - 10.3390/ijms23158538 [doi] LID - 8538 AB - The effects of psychological stress on eosinophilic gastrointestinal disorders have not been elucidated. This study investigated the effects of psychological stress in a mouse model of eosinophilic enteritis (EoN). BALB/c mice were treated with ovalbumin (OVA) to create an EoN model and subjected to either water avoidance stress (WAS) or sham stress (SS). Microscopic inflammation, eosinophil and mast cell counts, mRNA expression, and protein levels of type 2 helper T cell (Th2) cytokines in the ileum were compared between groups. We evaluated ex vivo intestinal permeability using an Ussing chamber. A corticotropin-releasing hormone type 1 receptor (CRH-R1) antagonist was administered before WAS, and its effects were analyzed. WAS significantly increased diarrhea occurrence and, eosinophil and mast cell counts, and decreased the villus/crypt ratio compared to those in the SS group. The mRNA expression of CRH, interleukin IL-4, IL-5, IL-13, eotaxin-1, and mast cell tryptase beta2 significantly increased, and the protein levels of IL-5, IL-13, and OVA-specific immunoglobulin E (IgE) also significantly increased in the WAS group. Moreover, WAS significantly increased the intestinal permeability. The CRH-R1 antagonist significantly inhibited all changes induced by WAS. Psychological stress exacerbated ileal inflammation via the CRH-mast cell axis in an EoN mouse model. FAU - Kanamori, Atsushi AU - Kanamori A AD - Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan. AD - Department of Gastroenterology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan. FAU - Tanaka, Fumio AU - Tanaka F AD - Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan. FAU - Ominami, Masaki AU - Ominami M AD - Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan. FAU - Nadatani, Yuji AU - Nadatani Y AUID- ORCID: 0000-0001-7081-8746 AD - Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan. AD - Department of Premier Preventive Medicine/MedCity21, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan. FAU - Fukunaga, Shusei AU - Fukunaga S AD - Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan. FAU - Otani, Koji AU - Otani K AUID- ORCID: 0000-0001-9075-6415 AD - Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan. FAU - Hosomi, Shuhei AU - Hosomi S AD - Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan. FAU - Kamata, Noriko AU - Kamata N AD - Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan. FAU - Nagami, Yasuaki AU - Nagami Y AD - Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan. FAU - Taira, Koichi AU - Taira K AD - Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan. FAU - Fujiwara, Yasuhiro AU - Fujiwara Y AD - Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan. LA - eng PT - Journal Article DEP - 20220801 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Interleukin-13) RN - 0 (Interleukin-5) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Corticotropin-Releasing Hormone) RN - 9015-71-8 (Corticotropin-Releasing Hormone) RN - Eosinophilic enteropathy SB - IM MH - Animals MH - *Corticotropin-Releasing Hormone/metabolism MH - Disease Models, Animal MH - Enteritis MH - Eosinophilia MH - Gastritis MH - Ileum/metabolism MH - Inflammation/metabolism MH - Interleukin-13/metabolism MH - Interleukin-5 MH - *Mast Cells/metabolism MH - Mice MH - RNA, Messenger/metabolism MH - Receptors, Corticotropin-Releasing Hormone/genetics/metabolism MH - Stress, Psychological/complications PMC - PMC9369025 OTO - NOTNLM OT - corticotropin-releasing hormone OT - eosinophilic enteritis OT - eosinophilic gastrointestinal disorders OT - eosinophils OT - intestinal permeability OT - mast cells OT - psychological stress COIS- Y.F. had grant support from DAIICHI SANKYO COMPANY, LIMITED (Tokyo, Japan) and EA Pharma Co., Ltd (Tokyo, Japan). EDAT- 2022/08/13 06:00 MHDA- 2022/08/16 06:00 PMCR- 2022/08/01 CRDT- 2022/08/12 01:12 PHST- 2022/07/07 00:00 [received] PHST- 2022/07/26 00:00 [revised] PHST- 2022/07/29 00:00 [accepted] PHST- 2022/08/12 01:12 [entrez] PHST- 2022/08/13 06:00 [pubmed] PHST- 2022/08/16 06:00 [medline] PHST- 2022/08/01 00:00 [pmc-release] AID - ijms23158538 [pii] AID - ijms-23-08538 [pii] AID - 10.3390/ijms23158538 [doi] PST - epublish SO - Int J Mol Sci. 2022 Aug 1;23(15):8538. doi: 10.3390/ijms23158538.