Browsing by Subject "Ulcerative colitis"
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- PublicationOpen AccessCytoglobin expression of rectal subepithelial myofibroblasts: Significant alterations of cytoglobin+ stromal cells in long-standing ulcerative colitis(F. Hernández y Juan F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología, 2011) Okayasu, Isao; Mikami, Tetuo; Yoshida, Tsutomu; Hana, Kiyomi; Yokozawa, Yokozawa; Sada, Miwa; Fujiwara, Mutsunori; Kawada, NorifumiCytoglobin/stellate cell activation-associated protein (Cygb/STAP), a hemoprotein, functions as part of an O2 reservoir with protective effects against oxidative stress in hepatic stellate cells. Heterogeneous expression of the neural cell adhesion molecule (NCAM)+ and/or α-smooth muscle actin (αSMA)+ has been noted in subepithelial myofibroblasts and interstitial cells of the same lineage in the colorectum. We have demonstrated that early genomic instability of both epithelial and stromal cells in ulcerative colitis (UC) is important for colorectal tumorigenesis, as well as for mucosal remodeling. To further clarify possible roles of stromal cells in mucosal remodeling and tumor development in UC, we here focused on Cygb expression of subepithelial myofibroblasts and interstitial cells, as well as αSMA and HSP47. Noncancerous mucosa of resected rectae from UC patients with or without colorectal neoplasia (14 and 20 cases, respectively) and of sporadic rectal cancer cases (16) was analyzed immunohistochemically, as well as by immuno-fluorescence and electron microscopy. The results, heterogeneous phenotypes of Cygb+, αSMA+ and HSP47+ subepithelial myofibroblasts and interstitial cells, corresponding to rectal stellate cells, were demonstrated. A decrease of Cygb+ subepithelial myofibroblasts and an increase of αSMA+ interstitial cells were significant in UC, as compared to normal rectal mucosa. Furthermore, a decrease of Cygb+ subepithelial myofibroblasts, correlating with αSMA+ and HSP47+ cells, was significant in long-standing UC with neoplasia. In conclusion, there are heterogeneous phenotypes of Cygb+, αSMA+ and HSP47+ subepithelial myofibroblasts and interstitial cells in the rectal mucosa. Mucosal remodeling with alterations of Cygb+ and/or αSMA+/HSP47+ stromal cells might have some relation to UC-associated tumorigenesis.
- PublicationOpen AccessDown-regulation of miR-215 attenuates lipopolysaccharide-induced inflammatory injury in CCD-18co cells by targeting GDF11 through the TLR4/NF-κB and JNK/p38 signaling pathways(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Sun, Boyang; Xing, Kai; Qi, Chen; Yan, Ke; Xu, YanUlcerative colitis (UC) is a risk factor for carcinogenesis of colorectal cancer, which is associated with disruption of the epithelial barrier and disorder of the inflammatory response. It has been reported that the expression of microRNA (miR)-215 is upregulated in patients with long-term UC. The present study aimed to investigate the effects of miR-215 on lipopolysaccharide (LPS)-induced inflammatory injury in CCD-18Co cells, as well as to identify the underlying possible molecular mechanisms. CCD-18Co cells were treated with 1 µg/ml LPS to induce inflammatory injury. Reverse transcription-quantitative PCR was performed to determine the expression of miR-215 in LPS-treated CCD-18Co cells. Moreover, a dual luciferase reporter system assay was used to evaluate the interaction of miR-215 and growth differentiation factor 11 (GDF11) in CCD-18Co cells. The expression of miR-215 was significantly upregulated in LPS-treated CCD-18Co cells. Knockdown of miR-215 significantly alleviated the inflammatory response and oxidative stress in LPStreated CCD-18Co cells. In addition, GDF11 was identified as a direct binding target of miR-215 in CCD18Co cells. Knockdown of miR-215 significantly increased the expression of GDF11, but decreased the expression levels of Toll-like receptor (TLR)4, phosphorylated (p)-p65, iNOS, p-p38 and p-JNK in LPS-treated CCD-18Co cells. Collectively, the present findings indicated that knockdown of miR-215 alleviated oxidative stress and inflammatory response in LPStreated CCD-18Co cells by upregulating GDF11 expression and inactivating the TLR4/NF-κB and JNK/p38 signaling pathways.
- PublicationOpen AccessExpression of WIF-1 in inflammatory bowel disease(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Terry, Robert; Chintanaboina, JayaKrishna; Patel, Deep; Lippert, Brittany; Haner, Matthew; Price, Kimberly; Tracy, Amanda; Lalos, Alexander; Wakeley, Michelle; Gutierrez, Linda S.The WNT/β-catenin cellular network has been extensively studied in numerous diseases including inflammatory bowel disease (IBD). IBD is a condition that increases the risk of developing colorectal cancer. WIF-1 is an inhibitory protein that acts by blocking the interactions of WNT with its receptor complex, thus leading to downregulation of end products of this pathway. While WIF-1 has been characterized in several cancers, its relationship with IBD has yet to be elucidated. In this study, the expression of WIF-1 in patients with IBD was analyzed in order to provide insights into the pathophysiology and rationale for alternative therapies. Biopsies of both normal and inflamed colonic mucosa from patients with Crohn’s disease or ulcerative colitis were histologically examined for the degree of morphologic changes, immune cell infiltration and presence of WIF-1 through immunohistochemistry. No differences were observed in WIF-1 expression linked to a particular condition, but WIF-1 stain was significantly enhanced in the crypts and lamina propria as inflammation increased in biopsies from patients with both, ulcerative colitis and Crohn’s disease. These findings could give guidance to new therapeutic applications of the WNT/β-catenin system and WIF-1 in IBD.
- PublicationOpen AccessGlucocorticoid receptor modulates dendritic cell function in ulcerative colitis(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Yang, Xinxin; Geng, JingshuUlcerative colitis (UC) is a serious form of inflammatory bowel disease (IBD) occurring worldwide. Although anti-TNF therapy is found to be effective in over 70% of patients with UC, nearly one-third are still deprived of effective treatment. Because glucocorticoids (GC) can effectively inhibit granulocyte-recruitment into the mucosa, cytokine secretion and T cell activation, they are used widely in the treatment of UC. However, remission is observed in only 55% of the patients after one year of steroid use due to a condition known as steroid response. Additionally, it has been noted that 20%-40% of the patients with UC do not respond to GC treatment. Researchers have revealed that the number of dendritic cells (DCs) in patients with UC tends to increase in the colonic mucosa. Many studies have determined that the removal of peripheral DCs through the adsorption and separation of granulocytes and monocytes could improve tolerance of the intestine to its symbiotic flora. Based on these results, further insights regarding the beneficial effects of Adacolumn apheresis in patients subjected to this treatment could be revealed. GC can effectively inhibit the activation of DCs by reducing the levels of major histocompatibility complex class II (MHC II) molecules, which is critical for controlling the recruitment of granulocytes. Therefore, alternative biological and new individualized therapies based on these approaches need to be evaluated to counter UC. In this review, progress in research associated with the regulatory effect of glucocorticoid receptors on DCs under conditions of UC is discussed, thus providing insights and identifying potential targets which could be employed in the treatment strategies against UC
- PublicationRestrictedKiller immunoglobulin-like receptor repertoire analysis in a Caucasian Spanish cohort with inflammatory bowel disease(Wiley, 2016-11) López Hernández, Ruth; Campillo, Jose Antonio; Valdés, Mariano; Salama, Hortensia; Boix, Francisco; Hernández Martínez, AM; Eguia, Jorge; González Martínez, G; Moya Quiles, María R.; Minguela, Alfredo; García Alonso, Ana; Carballo, Fernando; Muro, Manuel; Legaz Pérez, Isabel; Ciencias SociosanitariasImmunological molecules are implicated in inflammatory disorders, including inflammatory bowel disease (IBD; Crohn disease [CD] and ulcerative colitis [UC]). Killer cell immunoglobulin-like receptors (KIRs) are also genetically variable proteins involved in immune function. They are expressed by NK cells and certain T lymphocytes, regulate specificity and function by interaction with HLA Class I molecules, may be either inhibitory or activating and are polymorphic both in terms of alleles and haplotype gene content. Genetic associations between activating KIRs and certain autoimmune and inflammatory diseases have been reported; however, a possible association between KIR and IBD remains unclear. The aim of this study was to determine the relationship between KIR repertoire and IBD pathologies in a Spanish cohort. KIR variability was analyzed using PCR–sequence specific oligonucleotide probes (SSOP). Inhibitory KIR2DL5 was found more frequently in UC and IBD patient groups than in healthy controls (P = 0.028 and P = 0.01, respectively), as was activating KIR2DS1 (P = 0.02, Pc > 0.05, UC vs. Controls; P = 0.001, Pc = 0.01, IBD vs Controls; P = 0.01, Pc > 0.05, Controls vs CR), KIR2DS5 (P = 0.0028, Pc = 0.04, Controls vs UC; P = 0.0001, Pc = 0.0017, Controls vs IBD; P = 0.01, Pc > 0.05, Controls vs CD) and KIR3DS1 (P = 0.012, Pc > 0.05, Controls vs IBD). Our data suggest that imbalance between activating and inhibitory KIR may partially explain the different pathogeneses of these IBDs and that there is a hypothetical role for the telomeric B region (which contains both KIR2DS5 and KIR2DS1) in these diseases.
- PublicationOpen AccessThe role of activated cytotoxic T cells in inflammatory bowel disease(Murcia : F. Hernández, 2000) Kappeler, Andreas; Mueller, C.The role of cell-mediated cytotoxicity in the pathogenesis of ulcerative colitis and Crohn's disease has been controversial since reports indicating either a decreased, or an increased, activity of cytotoxic T cells in active stages of inflammatory bowel disease exist. Some of these discrepancies may be attributed to the fact that so far mostly peripheral blood lymphocytes rather than intestinal T cells have been examined. To overcome some of these limitations we performed in situ hybridizations for the detection of perforin and granzyme A mRNA expressing cells, i.e. of cytotoxic cells activated in situ, in the affected intestinal mucosa. These studies revealed increased frequencies of activated, cytotoxic T cells in active stages of ulcerative colitis and Crohn's disease. Interestingly, activated perforin mRNA expressing T cells are present both in the CD4 and in the CD8 T cell subsets. In the latter T cell subset up to 60% of the mucosal T cells isolated from the affected sites express perforin mRNA at detectable levels. The elevated frequency of activated cytotoxic cells and their histological distribution also in close proximity to the epithelial cells may thus indicate an important role for cytotoxic cells in the pathogenesis of inflammatory bowel disease since activated cytotoxic T cells may further exacerbate the inflammatory process through the production of pro-inflammatory cytokines such as interferon-y or tumor necrosis factor-a, but also through the release of pro-inflammatory cytokines and chemokines upon lysis of epithelial cells and the increased influx of lumina1 antigens at the site of epithelia1 erosions.
- PublicationOpen AccessUltrastructural study of inflammatory bowel disease(Murcia : F. Hernández, 1992) Mughal, S.; Filipi, M.I.Ultrastructural changes that occurred in chronic active ulcerative colitis and Crohn's disease were investigated and compared to normal as well as to higher grades of dysplasia in adenomas and carcinomas. A greater number of immature absorptive cells, undifferentiated and intermediate cells were seen as compared to normal. One case of Crohn's and two cases of chronic ulcerative colitis including one with coexisting carcinoma showed increased number of vesicles and electron-dense bodies (EDB) in the absorptive cells and increased heterogeneity of mucin droplets in goblet cells and presence of atypical secretory cells (ASC). Higher grades of dysplasia characterised by large numbers of atypical secretory cells were not seen in the present series and provide no relationship between the atypical ultrastructural features and increased risk of malignancy. However, the number of cases investigated is too small and a large series is required to clarify the significance of observations such as increased number of electron-dense bodies and vesicles in the apical cytoplasm and presence of atypical secretory cells.