Anti-CD3 induces bi-phasic apoptosis in murine intestinal epithelial cells: possible involvement of the Fas/Fas ligand system in different T cell compartments

Miura, Noriaki; Yamamoto, Masahiro; Fukutake, Masato; Ohtake, Nobuhiro; Iizuka, Seiichi; Ishige, Atsushi; Sasaki, Hiroshi; Fukuda, Kazunori; Yamamoto, Tatsuo; Hayakawa, Satoshi

doi:10.1093/intimm/dxh231

Cited by 23 publications

(35 citation statements)

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“…As we did not study the extrinsic apoptotic pathway in this study, an additive role of the extrinsic pathway could not be ruled out for our patients. However, keeping in mind the results of the previously published studies, [8][9][10][11][12][13][14] we can conclude that, along with the extrinsic pathway, the common as well as the intrinsic apoptotic pathways are active in treatment-naïve patients with celiac disease.…”

Section: Commentmentioning

confidence: 71%

“…6,12,[14][15][16] Van Der Woude et al 25 could not demonstrate enhanced apoptosis with immunohistochemical stains for active caspase-3, CK18, and apoptosis-related proteins Fas, iNOS, Bcl-2, Bcl-xl, and Bax in patients with celiac disease and thus the authors concluded that the loss of villi in active celiac disease may be the result of other unknown mechanisms. However, our results show the role of apoptosis in villous atrophy in celiac disease.…”

Section: Commentmentioning

confidence: 99%

“…[1][2][3][4][5] While a few studies have suggested a role for apoptosis in villous atrophy in patients with celiac disease, others do not confirm this finding. [6][7][8][9][10][11][12][13][14] In such a study, Moss et al 6 had reported presence of fragmented DNA in the intestinal mucosa of treatment-naïve patients with celiac disease, which disappeared after administration of gluten-free diet. Most other studies in this respect were limited to the identification of the role of FAS and FAS-Lmediated apoptosis.…”

mentioning

confidence: 99%

“…Most other studies in this respect were limited to the identification of the role of FAS and FAS-Lmediated apoptosis. [10][11][12][13][14] (2005) have identified the role of extrinsic apoptotic pathway activation in the mucosa of patients with celiac disease. On the other hand, apoptosis can be induced either by the extrinsic or the intrinsic apoptotic pathways.…”

mentioning

confidence: 99%

“…Moreover, most of the published literature has relied on the terminal deoxynucleotidyl transferase-deoxyuridine triphosphate nick-end labeling (TUNEL) method for identifying the apoptotic cells by immunofluorescence technique. 10,12,14 Considerable expertise is needed to apply and interpret this technique, especially for intestinal lesions.…”

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confidence: 99%

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Mechanism of Villous Atrophy in Celiac Disease: Role of Apoptosis and Epithelial Regeneration

Shalimar

Das

Sreenivas

et al. 2013

Archives of Pathology &Amp; Laboratory Medicine

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Context.—The data on status of apoptosis in patients with celiac disease are conflicting. Furthermore, complex interaction between intrinsic and common apoptotic pathways, apoptotic inhibitors, and epithelial cell proliferation is largely unclear for patients with celiac disease. Objectives.—To determine the role of apoptosis and epithelial cell regeneration in celiac disease. Design.—Twenty-five treatment-naïve patients with celiac disease and 6 patients with functional dyspepsia, as controls, were included and duodenal biopsy specimens from all were subjected to immunohistochemistry with markers of intrinsic apoptotic pathway (AIF, H2AX, p53), common pathway (CC3, M30), apoptotic inhibitors (XIAP, Bcl2), and epithelial proliferation (Ki-67). Apoptotic and proliferation indices were calculated. Results.—Expression of end-apoptotic products, that is, H2AX in the cell nuclei (P = .01) and M30 in the cell cytoplasm (P < .01), was significantly upregulated in celiac disease in comparison to controls. Cleaved caspase-3 was also upregulated in villous cytoplasm in celiac disease. Apoptotic inhibitor Bcl2 was significantly down-regulated in celiac disease in comparison to controls. In addition, Ki-67 proliferation index was upregulated both in the crypts and villous mucosal epithelium in comparison to the crypts of the controls. Conclusions.—Treatment-naïve patients with celiac disease have significantly higher level of apoptosis that involves both the common and intrinsic apoptotic pathways. Increased apoptosis and unequaled cell regeneration in crypts probably results in villous atrophy. Down-regulation of apoptotic inhibitors in treatment-naïve celiac disease imparts an additional pro-apoptotic effect.

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Section: Commentmentioning

confidence: 71%

Section: Commentmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Mechanism of Villous Atrophy in Celiac Disease: Role of Apoptosis and Epithelial Regeneration

Shalimar

Das

Sreenivas

et al. 2013

Archives of Pathology &Amp; Laboratory Medicine

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Elucidation of improving effects of a traditional Japanese herbal formula, hochuekkito, comprising Atractylodis rhizoma, on T‐cell‐mediated intestinal mucositis in mice

Endo

Utagawa

Nagai

et al. 2022

Traditional & Kampo Medicine

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Aim Hochuekkito has been used for gastrointestinal immune depression. Among its 10 herbal components, Atractylodis rhizoma (AtR) and Atractylodis lanceae rhizoma (ALR), and also Hedysari radix (HR) and Astragali radix (AR), can be interchanged based on the patient's symptoms. However, the difference between these formulas for improving gastrointestinal immune depression is not clear. The aim of this study was to compare the effect of AtR‐ and ALR‐hochuekkkito on a T‐cell‐mediated systemic and small intestinal mucosal inflammation model. We also analyzed the active ingredients and mechanism of action of AtR‐hochuekkito on the antiapoptotic effect in the Fas/FasL‐mediated signaling cascade on intestinal epithelial cells. Methods The effects of hochuekkito, lipophilic ingredients, and oligosaccharides on the systemic and small intestinal mucosal inflammation induced by anti‐CD3 antibody were analyzed. The effect of the AtR formula on mRNA expression of molecules related to the apoptotic signaling cascade was analyzed. Results AtR‐hochuekkito improved intestinal mucosal inflammation even if HR and AR were interchanged. Meanwhile, only the ALR formula suppressed systemic inflammation, whereas the AtR formula failed to improve it even if HR was replaced with AR. AtR formula administration increased gene mRNA expression of antiapoptotic regulatory adapter molecules in the small intestine of anti‐CD3 administered mice. The lipophilic ingredients in the AtR formula improved the effect on the small intestinal mucosal inflammation; liquiritin was an active ingredient. The intermediate‐size inulo‐oligosaccharides suppressed the recruitment of cytotoxic CD8 lymphocytes in the small intestine. Conclusion AtR‐hochuekkito is suitable for the treatment of small intestinal mucosal inflammation induced by spontaneous activation of T lymphocytes.

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Current Advances in Celiac Disease: Consequences and Improvement Strategies

Mukhopadhyay

2021

Challenges and Potential Solutions in Gluten Free Product Development

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Anti-CD3 induces bi-phasic apoptosis in murine intestinal epithelial cells: possible involvement of the Fas/Fas ligand system in different T cell compartments

Cited by 23 publications

References 31 publications

Mechanism of Villous Atrophy in Celiac Disease: Role of Apoptosis and Epithelial Regeneration

Mechanism of Villous Atrophy in Celiac Disease: Role of Apoptosis and Epithelial Regeneration

Elucidation of improving effects of a traditional Japanese herbal formula, hochuekkito, comprising Atractylodis rhizoma, on T‐cell‐mediated intestinal mucositis in mice

Current Advances in Celiac Disease: Consequences and Improvement Strategies

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