Study on improvement effects and mechanism of rhein on immunoglobulin A nephropathy / 中国药房

OBJECTIVE To study the improvement effects and mechanism of rhein on immunoglobulin A nephropathy （IgAN） model rat based on signal transducer and activator of transcription 3 （STAT3） signaling pathway. METHODS Rats were randomly divided into normal control group， IgAN model group and rhein treatment group， with 10 rats in each group. IgAN model group and rhein treatment group were given combination of bovine serum albumin+lipopolysaccharide+carbon tetrachloride to induce IgAN model. Since the 7th week， rhein treatment group rats were intragastrically given relevant medicine， and normal control group and model group rats were given equal amount of normal saline intragastrically， for consecutive 4 weeks. After the last administration， the count of urine sediment erythrocyte， 24 h-urine total protein （UTP）， the levels of immunoglobulin A （IgA） in serum and secretory immunoglobulin A （sIgA） in intestinal mucosa were detected. The pathological changes of Peyer’s patch in renal cortex and intestinal mucosa and IgA deposition in renal cortex were observed. The expressions of interleukin-17 （IL-17）， IL- 6 and transforming growth factor β （TGF-β） in Peyer’s patch of intestinal mucosa in rats were detected. The expressions of STAT3 and related orphan receptor γt （RORγt） mRNA in Peyer’s patch were detected. The expressions of p-STAT3 and RORγt proteins in Peyer’s patch were detected. RESULTS Compared with normal control group， the count of urine sediment erythrocyte， 24 h-UTP， the levels of IgA in serum and sIgA in intestinal mucosa were increased significantly in IgAN model group （P＜0.01）； enlarged renal corpuscles， dilated renal sacs， obvious intratubular mesangial hyperplasia and fibrosis were observed in renal cortex； the volume and germinal center of Peyer’s patch in intestinal mucosa increased； IgA deposition of renal cortex zxyylxk20220103） was obvious； the expressions of IL-17， IL-6 and TGF-β in Peyer’s patch， mRNA expressions of STAT3 and RORγt， protein expressions of p-STAT3 and RORγt were increased significantly （P＜0.01）. Compared with IgAN model group，above indexes were decreased significantly in rhein treatment group （P＜0.01）， pathological damage of renal cortex was improved， the volume of Peyer’s patch and germinal center of intestinal mucosa were reduced， and IgA deposition in renal cortex was weakened. CONCLUSIONS Rhein can improve IgAN model rats， the mechanism of which may be associated with inhibiting STAT3 signaling pathway and regulating immune function of Peyer’s patch in intestinal mucosa.

Research progress on intestinal immunoregulation and mechanism of Sijunzi Decoction polysaccharide / 中草药

Sijunzi Decoction polysaccharide (SJZDP) is the active component contributing to the function of intestinal immunoregulation, which is the highest content in Sijunzi Decoction. SJZDP can activate immunological response in peyer’s patch, mesenteric lymph nodes, intestinal epithelial cells and intestinal intraepithelial lymphocytes, but the mechanism is unknown. The reported mechanisms of SJZDP’s intestinal immunoregulation activity are related to its regulation of intestinal flora and polyamine signaling pathway. This review is to give a comprehensive summary of information regarding the intestinal immunoregulation of SJZDP and mechanism to help us take the action for reasonable clinical utilization and further researches.

Eosinophils Regulate Type 2 Immune Responses Following Infection with the Nematode Trichinella spiralis

Eosinophils are multifunctional leukocytes implicated in protection against helminth infections. Although eosinophils comprise between 1~5% of peripheral blood leukocytes, they primarily reside in the gastrointestinal tract under homeostatic conditions, and rapidly proliferate upon parasitic infection. Intestinal infection with Trichinella spiralis (T. spiralis) induces eosinophilia when the parasite enters the larval stages and larvae finally migrate to the skeletal muscle. Eosinophils are known to mediate parasite death through antibody-dependent cellular cytotoxicity. In this study, we aimed to address the functional significance of eosinophils in the intestinal phase of T. spiralis infection by analysis of immune responses in the Peyer's patch (PP) of infected BALB/c and eosinophil-ablated ΔdblGATA mice. Trafficking of eosinophils to the PP was significantly increased, with upregulation of interleukin-5 at 14 days post infection. Eosinophil deficiency led to a significant augmentation of serum immunoglobulin (Ig) M and IgG1 antibody levels. In accordance with this, IgG1+ B cells in the PP were substantially increased in ΔdblGATA mice compared to that in BALB/c mice. Transforming growth factor-β expression in the PP of infected ΔdblGATA mice was significantly decreased compared to that in BALB/c mice, whereas the number of T. spiralis larvae in the diaphragm was increased. Taken together, these findings indicate that eosinophils contribute to the regulation of Th2 immune responses, and protect the host from T. spiralis attempting to establish larvae in the skeletal muscle.

Narrow-band imaging with magnifying endoscopy for Peyer's patches is useful in predicting the recurrence of remissive patients with ulcerative colitis

BACKGROUND/AIMS: Peyer's patches (PPs) are aggregates of lymphoid follicles that are mainly located in the distal ileum; they play a major role in mucosal immunity. We recently reported that patients with ulcerative colitis (UC) have alterations in PPs that can be detected using narrow-band imaging with magnifying endoscopy (NBI-ME). However, the usefulness of NBI-ME in UC treatment as a whole is still unknown. METHODS: We collected NBI-ME images of PPs from 67 UC patients who had undergone ileocolonoscopy. We evaluated changes in the villi using the "villi index," which is based on three categories: irregular formation, hyperemia, and altered vascular network pattern. The patients were divided into two groups on the basis of villi index: low (L)- and high (H)-types. We then determined the correlation between morphological alteration of the PPs and various clinical characteristics. In 52 patients who were in clinical remission, we also analyzed the correlation between NBI-ME findings of PPs and clinical recurrence. RESULTS: The time to clinical recurrence was significantly shorter in remissive UC patients with H-type PPs than in those with L-type PPs (P<0.01). Moreover, PP alterations were not correlated with age, sex, disease duration, clinical activity, endoscopic score, or extent of disease involvement. Multivariate analysis revealed that the existence of H-type PPs was an independent risk factor for clinical recurrence (hazard ratio, 3.3; P<0.01). CONCLUSIONS: UC patients with morphological alterations in PPs were at high risk of clinical relapse. Therefore, to predict the clinical course of UC, it may be useful to evaluate NBI-ME images of PPs.

Narrow-band imaging with magnifying endoscopy for Peyer's patches is useful in predicting the recurrence of remissive patients with ulcerative colitis

BACKGROUND/AIMS: Peyer's patches (PPs) are aggregates of lymphoid follicles that are mainly located in the distal ileum; they play a major role in mucosal immunity. We recently reported that patients with ulcerative colitis (UC) have alterations in PPs that can be detected using narrow-band imaging with magnifying endoscopy (NBI-ME). However, the usefulness of NBI-ME in UC treatment as a whole is still unknown. METHODS: We collected NBI-ME images of PPs from 67 UC patients who had undergone ileocolonoscopy. We evaluated changes in the villi using the "villi index," which is based on three categories: irregular formation, hyperemia, and altered vascular network pattern. The patients were divided into two groups on the basis of villi index: low (L)- and high (H)-types. We then determined the correlation between morphological alteration of the PPs and various clinical characteristics. In 52 patients who were in clinical remission, we also analyzed the correlation between NBI-ME findings of PPs and clinical recurrence. RESULTS: The time to clinical recurrence was significantly shorter in remissive UC patients with H-type PPs than in those with L-type PPs (P<0.01). Moreover, PP alterations were not correlated with age, sex, disease duration, clinical activity, endoscopic score, or extent of disease involvement. Multivariate analysis revealed that the existence of H-type PPs was an independent risk factor for clinical recurrence (hazard ratio, 3.3; P<0.01). CONCLUSIONS: UC patients with morphological alterations in PPs were at high risk of clinical relapse. Therefore, to predict the clinical course of UC, it may be useful to evaluate NBI-ME images of PPs.

<b>Oral Administration of the Potato Peel Extract Affects Cytokine Production in Murine Peyer’s Patch Cells</b> / 日本補完代替医療学会誌

We investigated the effects of an ethanol extract of potato peel on T helper cytokines production in cultured murine Peyer’s patch cells ex vivo. Oral administration of the 70% ethanol extract at 100 mg/kg/day significantly enhanced the production of the Th1 cytokine IL-2 in response to concanavalin A. A decrease in the production of the Th2 cytokine IL-4 and the Th17 cytokine IL-17 was observed. The production of the Treg cytokine IL-10 was not affected. These results suggest that the potato peel extract stimulates Th1 immune response.

C6, a new monoclonal antibody, reacts with the follicle-associated epithelium of calf ileal Peyer's patches

The follicle-associated epithelium (FAE) of Peyer's patches (PPs) contains M cells that are important for reducing mucosal immune responses by transporting antigens into the underlying lymphoid tissue. We generated a monoclonal antibody (C6) that reacted with the FAE of calf ileal PPs, and analyzed the characteristics of C6 using immunohistochemistry and Western blotting. FAE of the ileal PP was stained with C6 during both late fetal developmental and postnatal stages. Neither the villous epithelial cell nor intestinal crypt basal cells were stained at any developmental stage. During the prenatal stages, FAE of the jejunal PP was C6-negative. However, a few C6-positive cells were distributed diffusely in some FAE of the jejunal PPs during the postnatal stages. The protein molecular weight of the antigen recognized by C6 was approximately 45 kDa. These data show that C6 is useful for identifying the FAE in ileal PPs and further suggest that differentiation of the FAE in these areas is independent of external antigens.

C6, a new monoclonal antibody, reacts with the follicle-associated epithelium of calf ileal Peyer's patches

The follicle-associated epithelium (FAE) of Peyer's patches (PPs) contains M cells that are important for reducing mucosal immune responses by transporting antigens into the underlying lymphoid tissue. We generated a monoclonal antibody (C6) that reacted with the FAE of calf ileal PPs, and analyzed the characteristics of C6 using immunohistochemistry and Western blotting. FAE of the ileal PP was stained with C6 during both late fetal developmental and postnatal stages. Neither the villous epithelial cell nor intestinal crypt basal cells were stained at any developmental stage. During the prenatal stages, FAE of the jejunal PP was C6-negative. However, a few C6-positive cells were distributed diffusely in some FAE of the jejunal PPs during the postnatal stages. The protein molecular weight of the antigen recognized by C6 was approximately 45 kDa. These data show that C6 is useful for identifying the FAE in ileal PPs and further suggest that differentiation of the FAE in these areas is independent of external antigens.

Nuts 'n' guts: transport of food allergens across the intestinal epithelium

The increase in the incidence of food allergy is a growing problem for the western world. This review will focus on the findings from several macromolecular epithelial transport experiments and drug permeability studies to provide a recent comprehension of food allergen intestinal epithelial cell transport and the allergen-epithelial relationship. Specifically, this review will aim to answer whether allergens can permeate the intestinal barrier directly via intestinal epithelial cells, and whether this mode of transport affects downstream immune reactions. By improving our understanding of the interactions which take place during exposure of food allergens with the intestinal epithelium, we can begin to understand whether the epithelial barrier plays a major role in the allergic sensitization process rather than simply restricting the entry of allergens to the underlying lamina propria.

Ultrastructural Changes of Epithelium Covering Peyer's Patch by Simple Obstruction of Gerbil Ileum / 체질인류학회지

The light and electron microscopic studies were carried out to find the morphological changes of epithelial cells covering Peyer's patch after simple observation of gerbil (Mongolian gerbil) ileum. Animals were classified as the control, 6 hour-ligation and 18 hour-ligation groups. Terminal ileum was ligated with white silk around Peyer's patch without the vascular injury. In control group, epithelia of the gerbil ileum was consisted of villous epithelium and follicle-associated epithelium (FAE) covering Peyer's patch. FAE represented typical dome structure, and was composed of the cuboid absorptive cells mainly and M cells. M cells were distributed at the periphery rather than central portion of dome-like FAE that are distinguishable from absorptive cells, owing to their typically short and thick microvilli on its free surface. In the light mictoscopy on 6 hour-ligation group, cells with vacuoles were appeared in FAE, and some lymphocytes in lymphoid follicle were condensed and then densely stained. There are many lymphocytes in FAE, infiltrated through the interrupted basement membrane. In the electron microscopic findings of 6-hour-ligated group, absorptive cells appeared to have many vesicle and vacuoles in various size, some lipid droplets and membranous structure contained inclusion bodies. Microvilli of M cell appeared to be destroyed at the central portion on its free surface. In the light microscopy of 18 hour-ligation group, FAE destructed partially and lymphoid follicle was hypertrophied and atrophied simultaneously. In the electron microscopic findings of 18 hour-ligation group, absorptive cells appeared to have the irregular and densely stained nucleus, and have many lipid droplets other than structures observed in 6 hour-ligation group. M cell appeared to have various-sized vacuoles, and have the bleb-like and irregular membrane-limited structures that protrude into the lumen and have less the cytoplasmic cell organs. These results suggested that the simple ligation of ileum gives rise to the inflammatory response on FAE of 6 hourligated group and then lead to the various response; degeneration, necrosis and atrophy of cells in FAE, and the hypertrophy and atrophy of lymphocytes in lymphoid follicle. M cell might have no special function and have the degenerative change with the adjacent absorptive cells during simple obstruction.

Role of murine Peyer's patch lymphocytes against primary and challenge infections with Cryptosporidium parvum

In order to determine the role of Peyer's patch lymphocytes (PPL) in self-clearing of Cryptosporidium parvum infection in murine models, changes in PPL subsets, their cytokine expression, and in vitro IgG1 and IgA secretions by PPL were observed in primary- and challenge-infected C57BL/6 mice. In primary-infected mice, the percentages of CD4+ T cells, CD8+ T cells, sIgA+ B cells, IL-2+ T cells, and IFN-gamma+ T cells among the PPL, increased significantly (P 0.05) than those in primaryinfected mice. The results suggest that murine PPL play an important role in self-clearing of primary C. parvum infections through proliferation of CD4+, CD8+, IL-2+, and IFN-gamma+ T cells, and IgG1 and IgA-secreting B cells. In challenge infections, the role of T cells is reduced whereas that of B cells secreting IgA appeared to be continuously important.

Morphological Study of the Alterations of Lymphocytes of Rat Peyer's Patch by Dehydration / 체질인류학회지

Light and electron microscopic studies were performed to investigate the subcellular alterations of lymphocytes in rat Peyer's patches by dehydration. Sprague -Dawley rats weighing 210 to 230 gm were fed with dried diet and without water for 5, 7, 9, or 13 days. In light microscopy, the lymphocytes with very dark nucleus and/or cytoplasmic materials are shown in Peyer's patches of the dehydrated rats. The number of these lymphocytes were increased according to the degree of dehydration. Some dark nuclei were C or O shaped, and some cells with dark nucleus showed the light or empty cytoplasm as halo. The number of Tunel -positive lymphocytes were increased according to the duration of dehydration, and lymphocytes with Tunel -positive nucleus appeared in a group. some cells included the Tunel - positive nuclei and materials in their cytoplasm. Especially the cells of 13 day -dehydrated group had the strongly positive nucluei. In electron microscopy, the nuclei of lymphocytes shown very dark in light microscopy were condensed and/or fragmented. The aspects of nuclear condensations were various; simply condensed, rosary -like, crescentic or irregular. The destructions of cytoplasmic organelles were increased according to the degree of the dehydration. Many cells contained the phagosomes and necrotic and/or apoptosis -like cell debris, and the number of foreign body containing cells were increased according to the duration of the dehydration. These results showed that a number of lymphocytes were destructed by the necrosis and apoptosis -like mechanism morphologically, and the number of the cells containing these destructed cell debris are increased according to the duration of dehydration.