title: Interleukin-18 is a crucial determinant of vulnerability of the mouse rectum to psychosocial stress.
abstract: Psychosocial factors are important determinants of disease manifestations, treatment efficacy, and prognosis of functional and inflammatory bowel disorders. Isolation of C57BL/6J mice from their 4 brothers growing in the same cage reduced goblet cells and MUC2 expression with a peak on day 8 in the rectum, but not in the colon. Gene expression analysis using a whole mouse genome microarray showed that the stress induced a 10-fold larger change in the gene expression in the rectum (722 genes) than in the colon (72 genes). The Ingenuity Pathway Analysis (IPA) application organized the rectum-specific 711 genes into stress response-related pathways. Nuclear factor-kappaB-related cytokine networks constructed with IPA showed selective up-regulation of interleukin (IL)-18 mRNA expression, which was also confirmed by real-time polymerase chain reaction. The stress produced active forms of caspase 1, IL-18, and a negative regulator for goblet cells, Notch 1, only in the rectum. IL-18-knockout mouse rectum had significantly increased goblet cells and MUC2 mucin, compared with wild-type mouse rectum. The absence of IL-18 completely blocked the stress-induced changes in gene expression and the goblet cell responses in the rectum. Thus, IL-18 may be a crucial determinant for the vulnerability of the rectum to psychosocial stress.
authors.affiliation: Department of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Nishida
authors.forename: Mai
authors.initials: M
authors.lastname: Kamizato
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kawai
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Masuda
authors.forename: Keiko
authors.initials: K
authors.lastname: Takeo
authors.forename: Shigetada
authors.initials: S
authors.lastname: Teshima-Kondo
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Rokutan
mesh_terms: D000818:Animals; D003106:Colon / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D020397:Goblet Cells / Q000166:cytology / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D055262:Mucin-2 / Q000235:genetics / Q000378:metabolism; D012007:Rectum / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D012934:Social Isolation; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D020382:Interleukin-18; C524626:Muc2 protein, mouse; D055262:Mucin-2