The Expression Patterns of Toll-Like Receptors in the Ileal Pouch Mucosa of Postoperative Ulcerative Colitis Patients

Toiyama, Yuji; Araki, Toshimitsu; Yoshiyama, Shigeyuki; Hiro, Jun-ichiro; Miki, Chikao; Kusunoki, Masato

doi:10.1007/s00595-005-3144-y

Cited by 86 publications

(61 citation statements)

References 14 publications

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“…Similar to our findings of increased epithelial TLR4 and unchanged TLR5 expression in experimental NEC, there is increased enterocyte-specific expression of TLR4 and decrease of TLR5 expression in UC and CD (18,19) and in the DSS model of colitis (20). However, in our experimental NEC model, TLR4 deficiency appears to be clearly protective, while in a murine model of colitis, the role of TLR4 is less clear.…”

Section: Discussionsupporting

confidence: 72%

The Roles of Bacteria and TLR4 in Rat and Murine Models of Necrotizing Enterocolitis

Jilling

Simon

Lü

et al. 2006

The Journal of Immunology

354

330

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Bacteria are thought to contribute to the pathogenesis of necrotizing enterocolitis (NEC), but it is unknown whether their interaction with the epithelium can participate in the initiation of mucosal injury or they can act only following translocation across a damaged intestinal barrier. Our aims were to determine whether bacteria and intestinal epithelial TLR4 play roles in a well-established neonatal rat model and a novel neonatal murine model of NEC. Neonatal rats, C57BL/6J, C3HeB/FeJ (TLR4 wild type), and C3H/HeJ (TLR4 mutant) mice were delivered by Cesarean section and were subjected to formula feeding and cold asphyxia stress or were delivered naturally and were mother-fed. NEC incidence was evaluated by histological scoring, and gene expression was quantified using quantitative real-time PCR from cDNA generated from intestinal total RNA or from RNA obtained by laser capture microdissection. Spontaneous feeding catheter colonization or supplementation of cultured bacterial isolates to formula increased the incidence of experimental NEC. During the first 72 h of life, i.e., the time frame of NEC development in this model, intestinal TLR4 mRNA gradually decreases in mother-fed but increases in formula feeding and cold asphyxia stress, correlating with induced inducible NO synthase. TLR4, inducible NO synthase, and inflammatory cytokine induction occurred in the intestinal epithelium but not in the submucosa. NEC incidence was diminished in C3H/HeJ mice, compared with C3HeB/FeJ mice. In summary, bacteria and TLR4 play significant roles in experimental NEC, likely via an interaction of intraluminal bacteria and aberrantly overexpressed TLR4 in enterocytes.

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Section: Discussionsupporting

confidence: 72%

The Roles of Bacteria and TLR4 in Rat and Murine Models of Necrotizing Enterocolitis

Jilling

Simon

Lü

et al. 2006

The Journal of Immunology

354

330

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“…In a recent study, Toyama et al reported that toll-like receptor 2 (TLR-2) and toll-like receptor 4 (TLR-4) were strongly up-regulated in the mucosa of active pouchitis, while TLR-3 and TLR-5 expression was not detectable in the pouch mucosa, in the presence or absence of inflammation. 19 In one of our recent studies, we confirmed that high mucosal TLR-2 and TLR4 mRNA levels were associated to chronic/relapsing pouchitis. 16 TLR-2 recognizes and binds to fragments of bacterial peptidoglycan (the main component of bacterial cell wall), while TLR-4 recognizes and binds to bacterial lipopolysaccharides (LPS), endotoxins found in the outer membrane of gramnegative bacteria.…”

Section: Introductionsupporting

confidence: 84%

Innate Immune Environment in Ileal Pouch Mucosa: α5 Defensin Up-regulation as Predictor of Chronic/Relapsing Pouchitis

Scarpa

Grillo

Scarpa

et al. 2012

Journal of Gastrointestinal Surgery

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Defensins are small cationic peptides with antibacterial activity expressed in Paneth cells (α-defensins) or generally in intestinal epithelial cells (β-defensins) that have a profound effect on gut microbiota. Chronic pouchitis, which occurs in 5% of patients after restorative proctocolectomy and can cause pouch failure, is associated to a significant increase of Clostridiaceae spp. The aim of this study was to gain further insight in the pathogenesis of pouch dysbiosis by exploring defensin expression. Thirty-two consecutive patients coming for follow-up endoscopy were recruited. On pouch biopsies, we cultured bacteria adherent to the mucosa and determined α- and β-defensins and toll-like receptor-4 and -2 mRNA by quantitative real-time RT-PCR. Serum and mucosal levels of IL-1β, IL-6 and TNF-α were measured with immunometric assays. Faecal lactoferrin was analysed by quantitative ELISA. After a median follow-up of 23 (IQR 20-24) months, the patients were contacted for a reassessment of current and past disease activity. During the follow-up, chronic/relapsing pouchitis was diagnosed in six patients. The mucosal level of α-5 and α-6 defensins correlated with chronic/relapsing pouchitis onset (τ = 0.30, p = 0.034 and τ = 0.28, p = 0.053, respectively). High levels of α-5 defensin resulted to be predictive of chronic/relapsing pouchitis [AUC = 74% (95% CI = 53-89%), p = 0.052]. Patients with high levels of α-5 and α-6 defensins had earlier pouchitis relapses (p = 0.009 and p = 0.034, respectively). High levels of α-5 defensin were associated to a significant risk of chronic/relapsing pouchitis [OR = 10.6 (95% CI = 1.2-97.6), p = 0.027]. At multivariate analysis, the mucosal levels of α-5 defensin and the number of CFU of mucosa-associated Clostridiaceae spp resulted to be independent predictors of chronic/relapsing pouchitis [β = 0.46 (0.18), p = 0.024 and β = 0.44 (0.18), p = 0.027, respectively]. In conclusion, chronic/relapsing pouchitis is associated to increased expression of mucosal HD-5 and to increased antimicrobial activity against Escherichia coli. In patients with chronic/relapsing pouchitis, HD-5 and TLR-4 over-expression is likely to create a hostile environment against Enterobacteriaceae, thus favouring Clostridiaceae spp by decreasing competing bacteria families.

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“…In experiments with human IEC, TLR4 has been reported to be low and unresponsive to LPS (41,42). However, other investigators have shown constitutive expression of TLR4 in T84 cells and up-regulation of TLR4 in pouchitis (43,44). Redistribution of TLRs in IEC in association with inflammation has been observed, with transition from the apical to cytoplasmic compartments observed in polarized intestinal epithelium (43).…”

Section: Discussionmentioning

confidence: 91%

Toll-like Receptor 4 Mediates Induction of the Bcl10-NFκB-Interleukin-8 Inflammatory Pathway by Carrageenan in Human Intestinal Epithelial Cells

Bhattacharyya

Gill

Chen

et al. 2008

Journal of Biological Chemistry

151

129

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The Expression Patterns of Toll-Like Receptors in the Ileal Pouch Mucosa of Postoperative Ulcerative Colitis Patients

Cited by 86 publications

References 14 publications

The Roles of Bacteria and TLR4 in Rat and Murine Models of Necrotizing Enterocolitis

The Roles of Bacteria and TLR4 in Rat and Murine Models of Necrotizing Enterocolitis

Innate Immune Environment in Ileal Pouch Mucosa: α5 Defensin Up-regulation as Predictor of Chronic/Relapsing Pouchitis

Toll-like Receptor 4 Mediates Induction of the Bcl10-NFκB-Interleukin-8 Inflammatory Pathway by Carrageenan in Human Intestinal Epithelial Cells

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