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Paneth Cells (paneth + cell)
Selected AbstractsInfluence of standard treatment on ileal and colonic antimicrobial defensin expression in active Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009I. KÜBLER Summary Background, Crohn's Disease (CD), a chronic intestinal inflammation, is currently treated primarily by therapeutics which are directed against inflammatory responses. Recent findings though suggest a central role of the innate immune barrier in the pathophysiology. Important factors providing this barrier are antimicrobial peptides like the ,- and ,-defensins. Little is known about in vivo effects of common drugs on their expression. Aim, To analyse the influence of corticosteroids, azathioprine and aminosalicylate treatment on ileal and colonic antimicrobial peptides in active CD and also assess the role of inflammation. Methods, We measured the expression of antimicrobial peptides and pro-inflammatory cytokines in 75 patients with active CD. Results, Ileal and colonic ,- and ,-defensins as well as LL37 remained unaffected by corticosteroids, azathioprine or aminosalicylate treatment. Additionally, we did not observe a negative coherency between Paneth cell ,-defensins and any measured cytokines. HBD2 and LL37 unlike HBD1 levels were linked to inflammatory cytokines and increased in highly inflamed samples. Conclusions, Current oral drug treatment seems to have no major effect on the expression of antimicrobial peptides. In contrast to HBD2 and LL37, ileal levels of HD5 and HD6 and colonic HBD1 level are independent of current inflammation. Innovative drugs should aim to strengthen protective innate immunity. [source] Up-regulation of autophagy in small intestine Paneth cells in response to total-body ,-irradiation,,THE JOURNAL OF PATHOLOGY, Issue 2 2009Nikolai V. Gorbunov Abstract Macroautophagy (mAG) is a lysosomal mechanism of degradation of cell self-constituents damaged due to variety of stress factors, including ionizing irradiation. Activation of mAG requires expression of mAG protein Atg8 (LC3) and conversion of its form I (LC3-I) to form II (LC3-II), mediated by redox-sensitive Atg4 protease. We have demonstrated upregulation of this pathway in the innate host defense Paneth cells of the small intestine (SI) due to ionizing irradiation and correlation of this effect with induction of pro-oxidant inducible nitric oxide synthase (iNOS). CD2F1 mice were exposed to 9.25 Gy ,-ionizing irradiation. Small intestinal specimens were collected during 7 days after ionizing irradiation. Assessment of ionizing irradiation-associated alterations in small intestinal crypt and villus cells and activation of the mAG pathway was conducted using microscopical and biochemical techniques. Analysis of iNOS protein and the associated formation of nitrites and lipid peroxidation products was performed using immunoblotting and biochemical analysis, and revealed increases in iNOS protein, nitrate levels and oxidative stress at day 1 following ionizing irradiation. Increase in immunoreactivity of LC3 protein in the crypt cells was observed at day 7 following ionizing irradiation. This effect predominantly occurred in the CD15-positive Paneth cells and was associated with accumulation of LC3-II isoform. The formation of autophagosomes in Paneth cells was confirmed by transmission electron microscopy (TEM). Up-regulation of LC3 pathway in the irradiated SI was accompanied by a decreased protein,protein interaction between LC3 and chaperone heat shock protein 70. A high-level of LC3-immunoreactivity in vacuole-shaped structures was spatially co-localized with immunoreactivity of 3-nitro-tyrosine. The observed effects were diminished in iNOS knockout B6.129P2- NOS2tm1Lau/J mice subjected to the same treatments. We postulate that the observed up-regulation of mAG in the irradiated small intestine is at least in part mediated by the iNOS signalling mechanism. Published in 2009 by John Wiley & Sons, Ltd. [source] Rejection Reversibly Alters Enteroendocrine Cell Renewal in the Transplanted Small IntestineAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009T. M. Fishbein Acute small intestinal allograft rejection presents clinically as an abrupt increase in ileal fluid output in the absence of extensive inflammation. We questioned whether acute intestinal rejection might be accompanied by a disturbance of normal intestinal stem cell differentiation. We examined the intestinal epithelial secretory cell lineage among patients experiencing early rejection before and during rejection as well as following corrective therapy. Lineage-specific progenitors were identified by their expression of stage-specific transcription factors. Progenitors of the enteroendocrine cell (EEC) expressing neurogenin-3 (NEUROG3) were found to be disproportionately reduced in numbers, along with their more mature EEC derivatives expressing neuro D; the enteric hormone PYY was the most profoundly depleted of all the EEC products evaluated. No change in the numbers of goblet or Paneth cells was observed. Steroid treatment resulted in resolution of clinical symptoms, restoration of normal patterns of EEC differentiation and recovery of normal levels of enteric hormones. Acute intestinal rejection is associated with a loss of certain subtypes of EEC, most profoundly, those expressing PYY. Deficiency of the mature EECs appears to occur as a consequence of a mechanism that depletes NEUROG3 EEC progenitors. Our study highlights the dynamics of the EEC lineage during acute intestinal rejection. [source] Overexpression of interleukin-23, but not interleukin-17, as an immunologic signature of subclinical intestinal inflammation in ankylosing spondylitisARTHRITIS & RHEUMATISM, Issue 4 2009Francesco Ciccia Objective Subclinical gut inflammation is common in spondylarthritis, but the immunologic abnormalities underlying this process are undefined. Perturbation of the interleukin-23 (IL-23)/Th17 axis has emerged as a fundamental trigger of chronic inflammation. This study was undertaken to investigate the expression and tissue distribution of IL-23/Th17,related molecules in Crohn's disease (CD) and in subclinical gut inflammation in ankylosing spondylitis (AS). Methods Quantitative gene expression analysis of Th1/Th2 and IL-23/Th17 responses was performed in intestinal biopsy samples obtained from 12 patients with CD, 15 patients with AS, and 13 controls. IL-23 tissue distribution and identification of IL-23,producing cells were evaluated by immunohistochemistry. Results We demonstrated a strong and significant up-regulation of IL-23p19 transcripts in the terminal ileum in patients with AS and patients with CD. IL-23 was abundantly produced by infiltrating monocyte-like cells in inflamed mucosa from AS and CD patients. Notably, we also identified Paneth cells as a major source of IL-23 in patients with AS, patients with CD, and normal controls. Unlike CD, in AS patients, IL-23 was not associated with up-regulation of IL-17 and the IL-17,inducing cytokines IL-6 and IL-1,. Finally, while the Th1-related cytokines interferon-,, IL-12p35, and IL-27p28 were overexpressed only in CD patients, IL-4, IL-5, and STAT-6 were also significantly increased in AS patients. Conclusion Our findings indicate that overexpression of IL-23, but not IL-17, is a pivotal feature of subclinical gut inflammation in AS. Identification of resident Paneth cells as a pivotal source of IL-23 in physiologic and pathologic conditions strongly suggests that IL-23 is a master regulator of gut mucosal immunity, providing a pathophysiologic significance to the reported association between IL-23 receptor polymorphisms and intestinal inflammation. [source] The stem cells of small intestinal crypts: where are they?CELL PROLIFERATION, Issue 6 2009C. S. Potten Recently, there has been resurgence of interest in the question of small intestinal stem cells, their precise location and numbers in the crypts. In this article, we attempt to re-assess the data, including historical information often omitted in recent studies on the subject. The conclusion we draw is that the evidence supports the concept that active murine small intestinal stem cells in steady state are few in number and are proliferative. There are two evolving, but divergent views on their location (which may be more related to scope of capability and reversibility than to location) several lineage labelling and stem cell self-renewing studies (based on Lgr5 expression) suggest a location intercalated between the Paneth cells (crypt base columnar cells (CBCCs)), or classical cell kinetic, label-retention and radiobiological evidence plus other recent studies, pointing to a location four cell positions luminally from the base of the crypt The latter is supported by recent lineage labelling of Bmi-1-expressing cells and by studies on expression of Wip-1 phosphatase. The situation in the human small intestine remains unclear, but recent mtDNA mutation studies suggest that the stem cells in humans are also located above the Paneth cell zone. There could be a distinct and as yet undiscovered relationship between these observed traits, with stem cell properties both in cells of the crypt base and those at cell position 4. [source] Epithelial stem cell-related alterations in Trichinella spiralis -infected small intestineCELL PROLIFERATION, Issue 3 2009R. Walsh Objectives:, Infection of mice with the parasite Trichinella spiralis leads to small intestinal inflammation, characterized by changes in mucosal architecture and subpopulations of epithelial cells. This model has been used to explore changes in the epithelial proliferative cell population and expression of transforming growth factor-beta (TGF-,). Materials and methods:, Histochemical and immunohistochemical studies were undertaken in duodenal samples. Location and number of Ki-67-positive cells were assessed using Score and Wincrypts program. Changes in mRNA transcripts were studied by real-time RT-PCR. Results:,T. spiralis infection induced an increase in total number of proliferative (Ki-67-positive) cells per half crypt on day 2 post-infection. Transcription of Math1, a transcription factor required for secretory cell differentiation in the intestine, was up-regulated on days 6,18 post-infection. At these time points, numbers of Paneth cells at the crypt base were also increased and the epithelial proliferative zone was shifted up the crypt-villus axis. Transcription of TGF-, isoforms within the small intestine was up-regulated on days 6 and 12 post-infection, but anti-TGF-, antibody treatment had no effect on T. spiralis -induced changes in mucosal architecture or increase in Paneth/intermediate cells. Conclusions:,T. spiralis infection promotes an initial increase in small intestinal epithelial proliferation and subsequent cell differentiation along the secretory cell lineage. The resulting increase in numbers of Paneth cells at the crypt base causes the proliferative zone to move up the crypt-villus axis. Further studies are required to determine the significance of an increase in the expression of TGF-, transcripts. 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