Cellular Immune Response against Tropomyosin Isoform 5 in Ulcerative Colitis

Taniguchi, Masato; Geng, Xin; Glazier, Kenneth D.; Dasgupta, Arunansu; Lin, Jim Jung‐Ching; Das, Kiron M.

doi:10.1006/clim.2001.5133

Cited by 25 publications

(16 citation statements)

References 35 publications

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“…g, h Control section of infected mouse stomach stained with PBS instead of mAb CG3 reveals a minimal fluorescent background (h). Bar=30 μm colitis patients (Onuma et al 2000;Taniguchi et al 2001). A portion of hTM5 is detected on the surface of human colonic epithelial cells but not small intestinal epithelial cells (Kesari et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Accumulation of tropomyosin isoform 5 at the infection sites of host cells during Cryptosporidium invasion

O’Hara

Lin

2006

Parasitol Res

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The actin cytoskeleton of host cells has been implicated in Cryptosporidium invasion. However, the underlying mechanism of how actin filaments and associated proteins modulate this process remains unclear. In this study, we use in vitro cultured cell lines, human ileocecal adenocarcinoma HCT-8 and Chinese hamster ovary (CHO), and an in vivo mouse model to investigate the roles of tropomyosin isoforms in Cryptosporidium invasion. Using isoform-specific monoclonal antibodies, we found that the major human tropomyosin (hTM) isoforms expressed in HCT-8 cells are hTM4 and hTM5. HCT-8 cells also express hTM1 at low levels but not hTM2 and hTM3. During Cryptosporidium parvum infection, hTM5 colocalized to the infection sites with a novel parasite membrane protein, CP2. Neither hTM1 nor hTM4 accumulated at infection sites. Similarly, a high level of TM5 and varying amounts of TM4 accumulated at the C. parvum infection sites in CHO cells. CHO cells overexpressing hTM5 exhibit a significantly higher percent of mature meronts early in the infection process relative to CHO cells or CHO cells overexpressing a tropomyosin mutant, chimeric isoform hTM5/3. These results suggest that functional TM5 enhances Cryptosporidium invasion of host cells. In C. parvum-infected mice, accumulation and rearrangement of TM5 and TM4 were detected throughout the infected ileum. Similarly, in the Cryptosporidium muris-infected mice, TM5 accumulated in discrete regions of the epithelial cells of gastric glands and in the oocyst-laden stomach gland lumen. Cryptosporidium infection appears to rearrange and recruit host TM isoforms in both culture cells and in the mouse. Localized accumulation of tropomyosin at the infection sites may facilitate parasite invasion.

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Section: Discussionmentioning

confidence: 99%

Accumulation of tropomyosin isoform 5 at the infection sites of host cells during Cryptosporidium invasion

O’Hara

Lin

2006

Parasitol Res

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“…hTM isoform 5 (hTM5) is the predominant isoform in normal colon epithelium and it acts as an autoantigen in ulcerative colitis (UC) Geng et al 1998). We and others have shown that patients with UC demonstrate both humoral and cellular immune responses against hTM, particularly against isoform 5 (hTM5) Geng et al 1998;Onuma et al, 2000;Biancone et al, 1995 ;Sakamaki et al, 2000 ;Taniguchi et al, 2001). A K-ras mutation occurs relatively early in human carcinogenesis (Vogelstein et al, 1988), and it is detected in various types of human malignancies (Soh et al, 1993;Cooper 1995).…”

Section: Introductionmentioning

confidence: 99%

Effects of Helicobacter pylori Infection on the Histology, Cellular Phenotype, K-ras Mutations, and Cell Kinetics in Gastric Intestinal Metaplasia in Patients with Chronic Gastritis and Gastric Cancer

Watari¹,

Tanabe²,

Moriichi³

et al. 2011

Gastritis and Gastric Cancer - New Insights in Gastroprotection, Diagnosis and Treatments

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“…10,12,13 These hTM5-specific immunoglobulin G (IgG) auto antibodies show a direct pathogenic effect on the destruction of colonic epithelial cells. On the other hand genetic contribution in the disease is demonstrated by prevalence of CD in siblings.…”

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confidence: 99%

“…Therapies: As mentioned above, inflammation rooted either in misdirected immune response which may be ignited by diverse reasons, or in autoimmune reaction towards some gut antigen are the leading theories on etiology of IBD. [11][12][13]27 These reactions set off inflammation cascades which lead to disruption of the intestinal barrier layer. Therefore, most of the therapeutic approaches focus on inhibiting inflammation by using anti-inflammatory drugs, antibiotics, or by attenuating the inflammatory pathway by neutralizing one or other participating molecules of the inflammation reaction cascade or by cutting down the immune response by immunosuppression.…”

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confidence: 99%

Inflammatory Bowel Diseases: Current Therapeutic Approaches and Potential of Using Stem Cells

Srivastava¹

2017

JSRT

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Inflammatory bowel diseases (IBDs) are chronic and progressively deteriorating in nature without many promising curative treatments. Chronic inflammation of not well defined origins is considered to be the root cause of the problem which affects intestinal mucosa with or without transmural involvement. IBDs are divided in two main categories: Crohn's disease (CD) and ulcerative colitis (UC). While there is no long lasting cure for IBDs, current therapies can only reduce the causative inflammatory process with the hope to induce long-term remission. Treatment modalities for the IBDs are still evolving. The increased understanding of the underlying immunopathology has helped identify new targeted treatment options like immunosuppressive antibodies directed against signaling molecules. Use of stem cells, which are capable of modulating the immune system, can offer a long lasting relief to the patients suffering from the disease. The goal for stem cell-based therapy is to achieve long lasting cure, if not a permanent one. To achieve this, it would be desirable to obtain cell types, whether genetically modified or naturally occurring, having a high migratory ability in addition to homing ability into the afflicted parts of intestine. These cells should also have high in vivo survival potential, and then be able to regulate the immune reaction without provoking any response from the host's immune system and repair the injured tissue. Hematopoietic stem cells (HSC) and mesenchymal stromal cells (MSC) therapies are being investigated as a treatment for IBDs. MSC therapy is well tolerated and has minimal established side-effects compared to HSC therapy, which involves ablative chemotherapy. Several clinical studies using MSCs have been initiated and some early results suggest several inherent problems. In each study, optimization of MSC therapy appears to be the most urgent problem, which can be resolved only by scientifically unveiling the mechanisms of therapeutic action of stem cells. In this review, we summarize current therapies for IBDs and recent advances in the field of stem cell therapy, which offer promise to become the next generation treatment of choice.

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Cellular Immune Response against Tropomyosin Isoform 5 in Ulcerative Colitis

Cited by 25 publications

References 35 publications

Accumulation of tropomyosin isoform 5 at the infection sites of host cells during Cryptosporidium invasion

Accumulation of tropomyosin isoform 5 at the infection sites of host cells during Cryptosporidium invasion

Effects of Helicobacter pylori Infection on the Histology, Cellular Phenotype, K-ras Mutations, and Cell Kinetics in Gastric Intestinal Metaplasia in Patients with Chronic Gastritis and Gastric Cancer

Inflammatory Bowel Diseases: Current Therapeutic Approaches and Potential of Using Stem Cells

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