Background: Enteritis is one of the most frequently reported symptoms in piglets infected with porcine circovirus type 2 (PCV2), but the immunopathogenesis has not been reported. Objectives: This study examined the effect of a PCV2 infection on the intestinal mucosal immune function through morphological observations and immune-related molecular detection. Methods: Morphological changes within the ileum of piglets during a PCV2 infection were observed. The expression of the related-molecules was analyzed using a gene chip. The immunocyte subsets were analyzed by flow cytometry. The secretory immunoglobulin A (SIgA) content was analyzed by enzyme-linked immunosorbent assay. Results: The PCV2 infection caused ileal villus damage, intestinal epithelial cells exfoliation, and an increase in lymphocytes in the lamina propria at 21 days post-infection. Differentially expressed genes occurred in the defense response, inflammatory response, and the complement and coagulation cascade reactions. Most of them were downregulated significantly at the induction site and upregulated at the effector site. The genes associated with SIgA production were downregulated significantly at the induction site. In contrast, the expression of the Toll-like receptor-related genes was upregulated significantly at the effector site. The frequencies of dendritic cells, B cells, and CD8+T cells were upregulated at the 2 sites. The SIgA content decreased significantly in the ileal mucosa. Conclusions: PCV2 infections can cause damage to the ileum that is associated with changes in immune-related gene expression, immune-related cell subsets, and SIgA production. These findings elucidated the molecular changes in the ileum after a PCV2 infection from the perspective of intestinal mucosal immunity, which provides insights into a further study for PCV2-induced enteritis.
Kim, Jong-Yeup;Cha, Min-Ji;Park, Young-Seon;Kang, Jaeku;Choi, Jong-Joong;In, Seung Min;Kim, Dong-Kyu
Molecules and Cells
/
v.42
no.4
/
pp.345-355
/
2019
Eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most challenging problems in clinical rhinology. FZD5 is a receptor for Wnt5A, and its complex with Wnt5A contributes to activating inflammation and tissue modification. Nasal polyps and eosinophil/non-eosinophil counts are reported to be directly correlated. This study investigated the expression and distribution of FZD5, and the role of eosinophil infiltration and FZD5 in eosinophilic CRSwNP pathogenesis. The prognostic role of eosinophil levels was evaluated in seven patients with CRSwNP. Fifteen patients with CRS were classified based on the percentage of eosinophils in nasal polyp tissue. Methylated genes were detected using methylCpG-binding domain sequencing, and qRT-PCR and immunohistochemistry were used to detect FZD5 expression in nasal polyp tissue samples. The results showed that mRNA expression of FZD5 was upregulated in nasal polyps. FZD5 expression was significantly higher in nasal polyp samples from patients with eosinophilic CRSwNP than in those from patients with non-eosinophilic CRSwNP, as indicated by immunohistochemistry. Furthermore, inflammatory cytokine levels were higher in eosinophilic CRSwNP-derived epithelial cells than in normal tissues. In conclusion, FZD5 expression in nasal mucosal epithelial cells is correlated with inflammatory cells and might play a role in the pathogenesis of eosinophilic CRSwNP.
Jang Kyung Hoon;Kim Myong Dong;Lee Chang Hyeon;Yu Yun Cho
Journal of Physiology & Pathology in Korean Medicine
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v.17
no.5
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pp.1276-1280
/
2003
To investigate the effect of acupuncture at Zushanli (ST 36) in this study, gastric endocrine cells (G cell) by avidin-biotinylated complex (ABC) technique and histological examinations (HE; periodic acid schiff, PAS; alcian blue stain) of the stomach were perfomed at 1, 3, 6 weeks in normal rats. In other groups, omeprazole were fed for 1, 3, 6 weeks to compare with acupuncture effect. Acupuncture applied to the ST 36 acupoint and the administration of omeprazole increased G cell significantly at 1, 3, 6 weeks in time dependant manner. Furthermore, acupuncture applied to the other acupoint on GB 34 did not produce significant effect. When the common peronial nerve was dissected, acupuncture of ST 36 acupoint produced change of G cell. These data suggest that acupuncture at ST 36 increased G cell in point specific way and that effect was not related with surrounding nerve.
Mucosal epithelia sense external stress signals and transmit them to the intracellular cascade responses. Ribotoxic stress-producing chemicals such as deoxynivalenol (DON) or other trichothecene mycotoxins have been linked with gastrointestinal inflammatory diseases by Fusarium-contamination. The purpose of this study was to test the hypothesis that DON evokes the epithelial sentinel signals of RNA-dependent protein kinase (PKR) and early growth response gene 1 (EGR-1), which together contribute to the pro-inflammatory cytokine interleukin 8 (IL-8) in human intestinal epithelial cells. PKR suppression by the dominant negative PKR expression attenuated DON-stimulated interleukin-8 production. Moreover, 1L-8 transcriptional activation by DON was also reduced by PKR inhibition in the human intestinal epithelial cells. Treatment with the PKR inhibitor also suppressed EGR-1 promoter activity, mRNA and protein induction, although mitogen-activated protein (MAP) kinases such as extracellular signal-regulated protein kinases (ERK) 1/2, p38, c-Jun N-terminal Kinase (INK) were little affected or even enhanced in presence of a PKR inhibitor. These patterns were also compared in the EGR-1-suppressed cells, which showed much more suppressed production of 1L-8. All things taken into consideration, DON-activated sentinel signals of EGR-1 via PKR mediated interleukin-8 production in human intestinal epithelial cells, which provide insight into the possible general mechanism associated with mucosal inflammation as an intestinal toxic insult by ribotoxic trichothecene mycotoxins.
Purpose: Colitis is a condition associated with a spectrum of altered morphologic changes and cellular adhesion. E-cadherin plays a key role in the establishment and maintenance of epithelial tissue structure and cell-cell adhesion. The purpose of this study is to evaluate E-cadherin expression in colonic epithelium of various colitis in children. Methods: The expressions of E-cadherin were examined in 39 cases of colonic mucosal biopsy specimen using immunohistochemical staining. When more than 50 percent of cells exhibited uniformly the same intensity and pattern of immunostaining as the adjacent normal mucosa, the antigen expression was considered normal. Abnormal expression was defined when less than 50 percent of cells stained, when cells showed a heterogeneously weak or altered distribution, or when complete absence of staining was observed. Results: Fifteen cases with non-specific colitis (38.5%), 7 cases of with Crohn's disease (17.9%), 5 cases of infectious colitis and milk protein sensitive proctocolitis (12.8%), 3 cases of ulcerative colitis (7.7%), 2 cases of Henoch-Schonlein purpura colitis (5.1%), one case of Behcet's disease and ischemic colitis (2.6%) were included in this study. E-cadherin expression was decreased in all kinds of colitis. Reduced expression of E-cadherin was observed in 77 percent of cases. E-cadherin was weaker or no expression in reparative epithelium and "ulcer associated cell lineage". Conclusion: Altered expression of E-cadherin occurs during mucosal inflammation in any kinds of colitis. These changes may be involved in promoting cell migration during epithelial restitution of the gastrointestinal mucosa.
This experiment was performed to evaluate the morphological responses of the duodenal epithelial cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of Bacillus Calmette-Guerin (BCG). In the experimental groups, each mouse was inoculated with $1{\times}10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline or BCG (0.5 mL/25 g B.W.: $0.03{\times}10^8\sim0.32{\times}10^8$ CFU) were injected subcutaneously to the animals every other day, respectively. The day following the 7th injection of saline or BCG, each mouse was injected with a single dose of $0.7{\mu}Ci$/g of methyl-$^3H$-thymidine (25 Ci/mmol, Amersham Lab, England) through tail vein. Seventy minutes after the thymidine injection, animals were sacrificed, and duodenal tissues were taken and fixed in 10% neutral formalin. Deparaffinized sections were coated with autoradiographic emulsion EM-1 (Amersham Lab, England) in a dark room and dried and were placed in a light-tight box. The number of labeled epithelial cells in the duodenal mucosae (mean number of labeled epithelial cells per 3.5 mm length of mucosa) were observed and calculated. On the light microscopic study, duodenal mucosae had no severe morphological changes following the injection of BCG. In the tumor control and BCG treated groups, a number of small lymphocytes and eosinophile leucocytes are slightly increased as compared with those of the normal control ones. On the autoradiographic study, number of the labeled cells of normal control, tumor control and BCG-treated mice were 632.3 (${\pm}14.47$), 761.7 (${\pm}27.65$) and 505.0 (${\pm}17.09$) respectively. From the above results, BCG may suppress the DNA synthesis of the duodenal epithelial cells, but does not results severe structural defect on the duodenal mucosae. And it is suggested that BCG may greatly improve the anticancer therapy on certain kind of cancer.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.26
no.5
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pp.470-480
/
2000
The epithelium of odontogenic cyst seems to be in a specific status of cellular proliferation and cytodifferentiation. With the identification of various genes, which play essential roles in the specific stages of cellular proliferation and differentiation, the cellular conditions of odontogenic cyst epithelium need to be reevaluated. This study aimed to estimate the degree of proliferating, differentiating and apoptotic activities of odontogenic cyst epithelium using antisera of PCNA, Ki-67, MPM-2, transglutaminase C, heat shock protein 70 and $ApopTag$^{(R)}$. method in 19 cases of odontogenic cysts. Cellular changes of the cyst epithelium were measured by intensity of each immunohistochemical staining. Results were as follows: 1. The proliferating activity of the cyst epithelium was slightly lower than that of normal oral mucosal epithelium, with the use of primary antibodies against PCNA, Ki-67, and MPM-2. And the proliferating activity of the epithelium in OKC group was even higher than that of the epithelium in non-OKC group. 2. The odontogenic cysts showed weakly positive reaction with transglutaminase C, but strongly positive reaction with HSP 70. 3. Occasionally, only a few apoptotic cell was observed in the superficial keratin layer of OKC. 4. The hyperplastic cyst epithelium infiltrated with mild inflammatory cells showed diffusely positive reaction with different proliferating factors. From the above results, we presumed that the endogenous proliferating and differentiating activity of the cyst epithelium was slightly lower than that of normal oral mucosal epithelium, and also supposed that the cyst epithelium could be reactivated for the further proliferation by the exogenous factors, such as inflammatory reaction and any chemicophysical irritations.
Objectives This study investigated the effects of Cheongyeonsan for allergic rhinitis. Methods First, the GS/MS was used to analyze the effects of Cheongyeonsan by measuring inflammatory markers. Second, 3 groups of 10 6-week-old BALB/c mice were divided into Ctrl (no treatment), ARE (allergic rhinitis-induced without treatment), and CRT (allergic rhinitis-induced after Cheongyeonsan treatment) groups. Ovalbumin (OVA) was used as an antigen to induce allergic rhinitis and sensitization was performed by intraperitoneal injection of 0.1% OVA solution 21, 14, and 7 days before the onset of allergic rhinitis. Allergic rhinitis was induced by dropping OVA solution on the nasal cavity of each mouse for 5 days after the last sensitization. Seven days after the first induction, second induction was introduced by the same method. After making the section, MMP-9, substance P, $TNF-{\alpha}$, $NF-{\kappa}B$ p65, COX-2, iNOS and Nrf, apoptotic cells were observed by Masson trichrome staining, immunohistochemical staining, TUNEL of nasal mucosal tissues of each group. Results GC/MS results showed undecanoic acid. Masson trichrome results showed that the CRT group had less respiratory epithelial damage. Immunohistochemical staining showed CRT group had 58% decrease in MMP-9, 61% decrease in substance P, 55% decrease in $TNF-{\alpha}$, 38% decrease in $NF-{\kappa}B$ p65, 53% decrease in COX-2, 54% decrease in iNOS, 87% increase in Nrf compared to those of the ARE group. TUNEL showed a positive reaction of 84% increase in apoptotic cells greater than that of the ARE group. Conclusions Cheongyeonsan alleviates nasal mucosal damage and reduces inflammatory mediators from allergic rhinitis-induced mice.
Proceedings of the Korean Nutrition Society Conference
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1995.11b
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pp.11-34
/
1995
Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.
Modified organs for air respiration in Korean fish was reviewed in the following 6 Korean fishes: three mudskippers (Boleophthalmus pectinirostris, Periophthalmus modestus and P. magnuspinnatus), two mud loaches (Misgurnus mizolepis and M. anguillicaudatus), and a torrent catfish (Liobagrus mediadiposalis). Three mudskippers and a torrent catfish have a modified epidermis to in order to make up for the deficient oxygen supply. Their epidermis has abundant intraepithelial blood capillaries except dermal capillaries situated just beneath the stratum germinativum of the epidermis in B. pectinirostris. The epidermis was thick due to component of the following cells: two kinds of glands as a small mucous cells and a large club cells in L. mediadiposalis, voluminous cells (swollen cells) swollen by epidermal cells and a small mucous cells in B. pectinirostris, and only voluminous cells having no any glandular cells in P. modestus and P. magnuspinnatus. In Particular, the epidermis of the mudskippers appears to be a web-like structure due to the swollen epithelial cells. The dermal bulges are found in B. pectinirostris and they are situated at the skin covering the body, not appendage of all the fins and the sucking disc. Another modified organ in M. mizolepis and M. anguillicaudatus occurs in intestine and its mucosal epithelium has abundant blood capillaries.
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