[Severe case of Chlamydia pneumoniae pneumonia].
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Adult↗
Biomedical subjects
Yoshihide Fujiyama
Publications and source records attributed to Yoshihide Fujiyama.
Pro-inflammatory cytokine-induced matrix metalloproteinase-1 (MMP-1) secretion in human pancreatic periacinar myofibroblasts.
Matrix metalloproteinases (MMPs) are the proteases involved in the degradation of the extracellular matrix. MMP-1 is thought to be one of the key enzymes in fibrolysis, a process closely related to tissue remodeling. In the present study, we investigated MMP-1 secretion from human pancreatic periacinar myofibroblasts in response to pro-inflammatory cytokines IL-1beta and TNF-alpha. We also attempted to clarify the intracellular signaling pathways mediating the cytokine-induced MMP-1 secretion. MMP-1 secretion was measured by an enzyme-linked immunosorbent assay. MMP-1 molecules were analyzed by Western blotting. MMP-1 mRNA expression was evaluated by Northern blotting. IL-1l and TNF-alpha stimulated the MMP-1 secretion in a dose- and time-dependent manner. Ninety percent of MMP-1 was secreted as inactive form (pro-MMP-1). The effects of IL-1beta and TNF-alpha were significantly inhibited by PD98059 MEK/ERK inhibitor). In contrast, SB203580 (p38 MAPK inhibitor), GF109203X (PKC inhibitor), and PDTC (NF-kappaB inhibitor) did not alter the MMP-1 secretion induced by IL-1beta and TNF-alpha. These effects were also observed at them RNA level. In conclusion, in human pancreatic periacinar myofibroblasts, MMP-1 secretion was regulated by the pro-inflammatory cytokines via the MEK/ERK cascade. Thus, human pancreatic periacinar myofibroblasts may play an important role in the remodeling of damaged pancreatic tissue in chronic pancreatitis via MMP-1 secretion.
Anti-Inflammatory Agents, Non-Steroidal↗
Regulation of IL-11 expression in intestinal myofibroblasts: role of c-Jun AP-1- and MAPK-dependent pathways.
IL-11 inhibits the activation of NF-kappaB and induces the Th2 polarization of CD4+ T cells. The clinical utility of IL-11 is being investigated in Crohn's disease. However, physiological secretion of IL-11 in the intestine remains unclear. In this study, we investigated IL-11 secretion in human intestinal subepithelial myofibroblasts (SEMFs). Intestinal SEMFs were isolated from the human colonic mucosa. IL-11 secretion and mRNA expression were determined by ELISA and Northern blot analysis. The activating protein (AP)-1-DNA binding activity was evaluated by EMSA. IL-11 secretion was induced by IL-1beta and transforming growth factor (TGF)-beta1. These were also observed at the mRNA level. The EMSAs demonstrated that both IL-1beta and TGF-beta1 induced AP-1 activation within 2 h after stimulation, and a blockade of AP-1 activation by the recombinant adenovirus containing a dominant negative c-Jun markedly reduced the IL-1beta- and TGF-beta1-induced IL-11 mRNA expression. IL-1beta and TGF-beta1 induced an activation of ERK p42/44 and p38 MAP kinases, and the MAP kinase inhibitors (SB-202190, PD-98059, and U-0216) significantly reduced the IL-1beta- and TGF-beta1-induced IL-11 secretion. The upregulation of IL-11 mRNA by IL-1beta- and TGF-beta1 was also mediated by a p38 MAP kinase-mediated mRNA stabilization. The combination of IL-1beta and TGF-beta1 additively enhanced IL-11 secretion. Intestinal SEMFs secreted IL-11 in response to IL-1beta- and TGF-beta1. Mucosal IL-11 secretion might be important as an anti-inflammatory response in the pathogenesis of intestinal inflammation.
Adenoviridae↗
A novel diamino-pyridine derivative (IS-741) attenuates rat ileitis induced by trinitrobenzene sulfonic acid.
BACKGROUND: The etiology and pathogenesis of inflammatory bowel disease remain unknown. However, neutrophil infiltration into the inflammatory lesion is an important process in inflammatory bowel disease. In this study, we used rat trinitrobenzene sulfonic acid (TNBS) ileitis as a Crohn's disease model, and investigated the effects of oral IS-741 (which inhibits the expression of Mac-1, a cell adhesion molecule) on leukocyte-endothelial interactions. METHODS: Rat ileitis was induced by the intraluminal injection of a TNBS solution (160 mg/kg in 50% ethanol) at a site 10 cm proximal to the ileocecal valve. The rats then received oral IS-741 (50 mg/kg) or saline for 7 days. On the day 8 after the initial administration of IS-741 or saline, we determined the visible damage score, and assessed myeloperoxidase (MPO) activity. Concentrations of cytokines in the ileum, such as interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were assayed by enzyme-linked immunosorbent assay (ELISA). We also investigated the infiltration of polymorphonuclear cells and Mac-1 positive cells by histological examinations. RESULTS: The administration of IS-741 resulted in a significant reduction of the visible damage score, myeloperoxidase (MPO) activity, and mucosal IL-8 levels in the ileum as compared with the saline administration. IS-741 also dramatically reduced the infiltration of polymorphonuclear cells and Mac-1 positive cells into the inflamed lesions. CONCLUSIONS: These results indicate that the oral administration of IS-741 inhibits neutrophil infiltration into inflamed lesions, and is effective for attenuating rat TNBS ileitis. This new anti-inflammatory agent may be beneficial for the treatment of inflammatory bowel disease.
Animals↗
Matrix metalloproteinase-3 secretion from human colonic subepithelial myofibroblasts: role of interleukin-17.
BACKGROUND: Subepithelial myofibroblasts (SEMFs) play a role in extracellular matrix (ECM) metabolism in the colon. In this study, we investigated the effects of interleukin (IL)-17, IL-1beta, and tumor necrosis factor (TNF)-alpha on matrix metalloproteinase (MMP)-3 secretion in colonic SEMFs. METHODS: MMP-3 secretion and MMP-3 mRNA expression were determined by Western and Northern blotting, respectively. The secretion of tissue inhibitor of matrix metalloproteinase (TIMP)-1 was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: In human colonic SEMFs, MMP-3 secretion and MMP-3 mRNA expression were induced by IL-17, IL-1beta, and TNF-alpha. The effect of IL-17 was observed, but this was weak as compared with those induced by IL-1beta or TNF-alpha. A c-Jun/activating protein-1 (AP-1) inhibitor, curcumin, reduced the IL-17-, IL-1beta-, and TNF-alpha-induced MMP-3 mRNA expression, and mitogen-activated protein (MAP) kinase inhibitors (U0126, PD098059, and SB203580) also blocked MMP-3 secretion. There findings indicate a role for AP-1 and MAP kinases in cytokine-induced MMP-3 secretion. Furthermore, costimulation by IL-17 + IL-1beta and by IL-17 + TNF-alpha induced a marked increase in MMP-3 secretion. The costimulatory effects of these combinations were also observed for TIMP-1 mRNA expression and TIMP-1 secretion. CONCLUSIONS: Colonic SEMFs actively secreted MMP-3 in response to IL-17, IL-1beta, and TNF-alpha. This was coupled with TIMP-1 secretion. Colonic SEMFs may play an important role in ECM turnover via MMP secretion.
Blotting, Northern↗
Germinated barley foodstuff, a prebiotic product, ameliorates inflammation of colitis through modulation of the enteric environment.
BACKGROUND: Germinated barley foodstuff (GBF), which contains glutamine-rich protein and hemicellulose-rich fiber, exhibits therapeutic effects in ulcerative colitis; however, its mechanism is still under investigation. The aim of this study was to evaluate the anti-inflammatory effects of GBF on colitis in terms of the epithelial inflammatory response. METHODS: Mice with dextran sulfate sodium-induced colitis were used. The effects of GBF on the colitis were evaluated by measuring the body weight; disease activity; mucosal damage (histology, mucosal inflammatory parameters, nuclear factor kappa B [NFkB] activation, and signal transducer and activator of transcription 3 [STAT3]); serum interleukin 6 (IL-6) level; cecal short-chain fatty acids (SCFAs); and bile acid contents. RESULTS: GBF significantly prevented disease activity and body weight loss after induction of colitis. Serum IL-6 level and mucosal STAT3 expression were also significantly attenuated, with a conspicuous reduction of mucosal damage; NFkB activity showed the same tendency. Cecal butyrate content was significantly higher and, interestingly, GBF mice had lower bile acid concentrations than the control group. CONCLUSIONS: GBF has the potential to reduce the epithelial inflammatory response by depressing STAT-3 expression and inhibiting NFkB binding activity. These effects may be brought about by an increase of butyrate production and adsorption of bile acids.
Animals↗
Supplement of a chitosan and ascorbic acid mixture for Crohn's disease: a pilot study.
OBJECTIVE: Although the pathogenesis of Crohn's disease remains unclear, dietary fat is thought to exacerbate intestinal inflammation. Chitosan is a water-insoluble dietary fiber, and a chitosan and ascorbic acid mixture has been shown in rats to increase fecal fat excretion without affecting protein digestibility. However, it remains unclear whether a chitosan and ascorbic acid mixture is safe and effective for patients with Crohn's disease. We designed a pilot trial to investigate the tolerability and amount of fat excretion after the oral administration of a chitosan and ascorbic mixture for inactive Crohn's disease. METHODS: Eleven outpatients were given seven tablets daily of a chitosan and ascorbic mixture (chitosan was given at 1.05 g/d) for 8 wk. Patients did not interrupt their respective therapies for Crohn's disease. RESULTS: The bowel movements of most patients increased slightly during the study. Nutritional and inflammatory markers in patients did not differ before and after treatment. The chitosan and ascorbic acid mixture significantly increased the fat concentration in the feces during treatment. CONCLUSIONS: These results indicated that oral administration of a chitosan and ascorbic acid mixture in patients with Crohn's disease is tolerable and increases fecal fat excretion without affecting disease activity.
Adult↗
Combined effect of hydrogen peroxide induced oxidative stress and IL-1 alpha on IL-8 production in CaCo-2 cells (a human colon carcinoma cell line) and normal intestinal epithelial cells.
Oxidative stress, IL-1alpha, and IL-8 are known to contribute to mucosal inflammation of the gastrointestinal tract. We examined the IL-8 response after brief exposure to hydrogen peroxide induced oxidative stress in CaCo-2 cells (a human colon carcinoma cell line) and in human intestinal epithelial cells. In addition, we examined whether exposure to oxidative stress, followed by IL-1alpha, could modulate IL-8 production. A transient up-regulation of IL-8 mRNA expression was observed after hydrogen peroxide treatment. Hydrogen peroxide induced oxidative stress was also observed to promote IL-8 secretion. Exposure to hydrogen peroxide, followed by IL-1alpha, enhanced IL-8 production over that achieved with IL-1alpha alone. Thus, oxidative stress and IL-1alpha were observed to cooperatively enhance IL-8 production.
Caco-2 Cells↗
Alterations in the DNA binding activity of transcriptional factors activator protein-1, Sp1, and hepatocyte nuclear factor-1 in rat jejunum during starvation and refeeding.
BACKGROUND: The molecular processes leading to mucosal atrophy, regrowth, and functional changes with starvation and refeeding are largely unknown. There are many transcriptional factors that might be related to mucosal atrophy and proliferation. In contrast, we previously reported that H+/peptide transporter and aminopeptidase N messenger RNA in the intestinal mucosa were upregulated during starvation. Therefore, we selected and studied three transcriptional factors: activator protein (AP)-1, Sp1, and hepatocyte nuclear factor (HNF)-1, which not only play important roles for enterocytes proliferation, but also exist in promoter lesions of the brush border enzymes and peptide transporter. METHODS: In the present study, we performed electrophoretic mobility shift assays employing AP-1, Sp1, and HNF-1, and evaluated the changes in the DNA binding activities in rat jejunum during starvation and refeeding. RESULTS: Two days after starvation, the Sp1 binding activity was significantly decreased to 61.8% as compared with the control level, whereas AP-1 was 121.4% and HNF-1 was 77.5%. Two hours after refeeding, the AP-1 activity was significantly increased to 175.0% as compared with the control level, and the HNF-1 activity was significantly increased to 180.2%. In contrast, the decreased SP1 level did not recover until 24 h after refeeding. CONCLUSIONS: The DNA binding activities of these three transcriptional factors were significantly changed in the rat jejunum during starvation and refeeding. Our results provide insight into the molecular mechanisms of the transcriptional regulations associated with mucosal atrophy, regrowth, and functional changes of the jejunal epithelium in response to starvation and refeeding.
Animals↗
Enhancement of aquaporin-3 by vasoactive intestinal polypeptide in a human colonic epithelial cell line.
BACKGROUND: Vasoactive intestinal polypeptide (VIP) plays an important role in water transport in the intestine. Several specialized channels termed aquaporins (AQP) facilitate water transport in the gastrointestinal tract. Aquaporin-3 localizes to epithelial cells in the human small intestine and colon. However, the regulatory mechanisms underlying the functions of AQP3 remain unclear. To characterize the regulation of AQP3 expression by VIP, we studied messenger (m)RNA expression, protein expression and DNA binding activity in a human colonic epithelial cell line, HT-29. METHOD: Human colonic epithelial cells, HT-29, were incubated with VIP (10-12-10-7 M). The cells were treated with protein kinase-A (PK-A) inhibitors (H-89, H-9) or chloride channel-blockers (diphenylamine-2-carboxylate (DPC), 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPD)). The expression of AQP3 mRNA and protein was determined by Northern blot and Western blot, respectively. The DNA-binding activities of cyclic adenosine monophosphate (cAMP) response elements/activating transcription factor (CRE/ATF)) in the nuclear extract were determined by electrophoretic mobility shift assay. RESULTS: Aquaporin-3 mRNA was up-regulated at a concentration of 10-10 M VIP. The expression of AQP3 protein was enhanced at 3 h after addition of VIP. The PK-A inhibitors (H-89, H-9) inhibited the expression of AQP3 mRNA enhanced by VIP and cAMP. The gel shift assay of CRE/ATF in HT-29 cells revealed a single band. CONCLUSION: These results indicate that VIP upregulated the expression of AQP3 mRNA and protein, and that a cAMP-dependent pathway mediated this effect in a human colonic epithelial cell line, HT-29.
Aquaporin 3↗
Rapid absorption of luminal polyamines in a rat small intestine ex vivo model.
BACKGROUND AND AIM: Not only biosynthesis, but also uptake from the intestinal lumen, are important polyamine sources. However, there has been no information regarding dynamic polyamine transport in the small intestine. We evaluated polyamine uptake from the small intestine using a rat ex vivo model. METHODS: The organ block consisting of the small intestine and blood vessels was used. The isolated small intestine was placed in a warmed saline bath and perfused in a non-circulating manner via the superior mesenteric artery. Radio-labeled putrescine, spermidine or spermine (7.4 x 104 Bq), with 1.0 mL of phosphate buffer saline (pH 7.4) was instilled into the jejunal lumen for 1 min. Blood samples from the portal vein were collected and sample radioactivity was determined. In another experiment, an immunohistochemical study of polyamine was performed. RESULTS: After 14C-polyamine instillation, radioactivity in the portal vein samples immediately increased and then decreased gradually. The absorptive pattern did not differ among the three polyamines. The recovery rates from radioactivity at the portal vein among the three polyamines were approximately 61-76% during the initial 10 min after the administration of 14C-polyamine, and were not different from each other. Aminoguanidine, which inhibits putrescine degradation, significantly suppressed initial putrescine uptake and recovery percentage. The intraluminal administration of spermine caused an increase in the immunoreactivity of the spermine antibody in the intestinal villi. CONCLUSION: Luminal polyamines were rapidly absorbed by the intestinal mucosa and then subsequently transferred into the portal vein using a rat ex vivo model. The prior administration of aminoguanidine significantly inhibited initial putrescine transport into the portal vein.
Animals↗
Alteration of aquaporin mRNA expression after small bowel resection in the rat residual ileum and colon.
BACKGROUND: Diarrhea occurring after small bowel resection gradually improves due to intestinal adaptation. It is known that several water channels, termed aquaporins (AQP), are expressed in the gastrointestinal tract and facilitate water transport. However, the changes of AQP after bowel resection remain unclear. In the present paper, the alterations in AQP mRNA expression were investigated after a massive small bowel resection in the rat residual ileum and colon. METHODS: The 6-week-old male Sprague-Dawley rats (n = 15) underwent an 80% distal small bowel resection. The residual ileum and colon were dissected on postoperative day 1, 3, 5 or 7 (n= 3 on each day). Total RNA was purified from each mucosa, and the expressions of AQP and sodium-dependent glucose transporter (SGLT1) mRNA were analyzed by northern blot. The plasma vasoactive intestinal polypeptide (VIP) concentrations on the preoperative day and postoperative day 1 were assayed. RESULTS: In the residual small intestine, the expression of AQP-1 and AQP-3 mRNA increased significantly on postoperative day 1. The AQP-7 mRNA increased on postoperative day 3, but the AQP-4 mRNA did not change after the bowel resection. The SGLT1 mRNA gradually decreased after the bowel resection. In the colon, the expression of AQP-3 increased on postoperative day 1 and 7, but AQP-4 mRNA did not change after surgery. The AQP-8 mRNA levels increased slightly on postoperative day 7. Plasma VIP concentration did not change between preoperative day and postoperative day 1. CONCLUSIONS: These results indicate that several AQP, except for AQP-4, were up-regulated after a massive small bowel resection, and that AQP might play important roles during adaptation.
Animals↗
Nutritional benefits of enteral alanyl-glutamine supplementation on rat small intestinal damage induced by cyclophosphamide.
BACKGROUND: Glutamine is the principal fuel used by the small intestine. Although the parental administration of glutamine promotes intestinal mucosal growth, it is controversial whether enteral glutamine is effective against small intestinal damage caused by chemotherapy. To further evaluate the benefits of enteral supplementation, peptide and amino acid transporter functions must be considered. METHOD: Rats were given cyclophosphamide (CPM) intraperitoneally (300 mg/kg). Expression of the amino acid transporter, B0 and peptide transporter (PepT1) in the jejunal mucosa was initially examined by northern blot analysis. Rats received a bolus oral supplement of an alanine (1.22 g/kg/day) plus glutamine (2.0 g/kg/day) mixture, alanyl-glutamine (2.972 g/kg/day) or saline as a control, for 7 days after CPM administration. RESULTS: Levels of B0 mRNA remained unchanged at both 3 and 7 days after CPM administration. Conversely, PepT1 mRNA increased significantly after CPM administration, and reached 200% of the initial level 7 days later. In rats given alanyl-glutamine, the mucosal wet weight and protein content increased significantly with increasing villus height at 3 and 7 days, compared with the alanine plus glutamine mixture. The plasma glutamine concentration in the alanyl-glutamine group, but not the alanine plus glutamine mixture group, increased significantly compared with that in the saline group. CONCLUSION: Enteral supplementation with an alanyl-glutamine but not alanine plus glutamine mixture prevents intestinal damage, as demonstrated by increased peptide transport expression and an elevated plasma glutamine concentration after CPM administration.
Alanine↗
Collagenous gastritis in a young Japanese woman.
Collagenous gastritis, a counterpart of collagenous colitis, is a rare disorder with less than 20 cases reported in the literature. A case of collagenous gastritis in a Japanese woman in her early 20s who had been receiving treatment for atopic dermatitis and bronchial asthma is reported. The patient complained of repeated epigastric pain, and endoscopy revealed multifocal atrophic areas and scars in the gastric body. Biopsy specimens showed a thickened eosinophilic band-like structure with entrapped capillaries approximately 30-70 micro m thick beneath the surface epithelium. It was regarded as a collagen band because it was positive on Azan staining but negative on amyloid staining. This finding was accompanied by marked infiltration of mononuclear cells and eosinophils in the lamina propria; however, no evidence of lymphocytic gastritis was found. Helicobacter pylori infection was not detected and inflammatory cell infiltration was minimal in the mucosa without the collagen band. Immunohistochemical analysis revealed that the band was positive for type III and type VI collagen. The size of the collagen band did not change for 2 years. These findings suggest that subepithelial collagen deposition was due to an abnormal local immune response based on generalized allergic disorder.
Adult↗
MALT lymphoma at the base of the tongue developing without any background of immunodeficiency or autoimmune disease.
We report a very rare case of a mucosa-associated lymphoid tissue (MALT) lymphoma of the base of the tongue. A 61-year-old woman was admitted to our hospital for further examination of a 12 mm x 15 mm x 5 mm tongue tumor. Histological examination of the tumor revealed a marked lymphoepithelial lesion. Lymphoma cells expressed CD5(-), CD10(-), CD19(+), CD20(+) on the surface of the cells by fluorescence activated cell sorter, and the genotypic analysis of the tumor cells revealed the presence of immunoglobulin heavy chain rearrangement and the absence of BCL-2 gene rearrangement by southern blot hybridization. Furthermore, neither the t(11;18) (q21;q21) translocation nor trisomy 3 was detected in lymphoma cells by fluorescence in situ hybridization method. The tongue tumor was completely resected and no recurrence has been noted in the 13 months to date.
Antigens, CD↗
Identification of env CRF-10 among HIV variants circulating in rural western Kenya.
As part of a program to determine the genetic diversity of human immunodeficiency virus in rural Kenya, we carried out a molecular analysis of the C2-V3 region of HIV-infected blood samples obtained from 30 antenatal clinic attendees of seven health centers in western Kenya. Direct sequencing was carried out on the envelope C2-V3 region of proviral DNA. On phylogenetic analysis with reference strains, 20 were subtype Al, 2 were subtype D, 1 was subtype C, 1 was subtype G, 1 was CRF-10, 2A/D, 2A/C, and 2 were unclassified. The presence of CRF-10 and the great variety of subtypes and recombinants in such a limited sample size suggest that western Kenya may be a potential hotspot for HIV recombination in the country.
Adolescent↗
The effects of lectins on indomethacin-induced small intestinal ulceration.
Growth factors, such as epidermal growth factor and keratinocyte growth factor, have considerable therapeutic potential for repairing mucosal injury in the intestine when given systemically. Recently, several lectins have been shown to have trophic effects on the intestine when given orally. We examined the effects of phytohaemagglutinin (PHA) and concanavalin A (Con-A) on indomethacin-induced intestinal injury in rat. Five-week-old rats were randomized to four groups (n=5), and intestinal injury was induced by indomethacin injection in three of these groups. Elemental diet (ED) feeding was then commenced. The groups were thus ED feeding/indomethacin untreated (control group), ED feeding/indomethacin treated (ED group), 0.1% PHA-supplemented ED feeding/indomethacin treated (PHA group) and 0.1% Con-A-supplemented ED feeding/indomethacin treated (Con-A group). After 7 days of feeding, macroscopic inflammatory scores, mucosal permeability, myeloperoxidase (MPO) activities and cell proliferation were determined. Macroscopic inflammatory scores, mucosal permeability and MPO activities were significantly lower in both lectin groups than that in control group. Twenty-four hour excretion rate of phenolsulphonphthalein was significantly lower in both lectin groups than that in ED group. Cell proliferation of the small intestine was significantly increased by both lectins. Lectin supplementation can induce ulcer healing following indomethacin-induced damage.
Animals↗
Effects of the soluble fibre pectin on intestinal cell proliferation, fecal short chain fatty acid production and microbial population.
AIM: Although pectin, a dietary fibre, has been suggested to possess some trophic effects on the intestine, the mechanisms involved remain unclear. This study aimed to evaluate the effects of pectin on rat intestinal cell proliferation and the intraluminal environment. METHODS: Control and pectin-fed rats were given a fibre-free elemental diet (ED) and an ED containing 2.5% pectin, respectively. On the 15th day, the length, weight and number of Ki-67-positive cells from each intestinal segment, and the short chain fatty acids (SCFAs) and microbial population in the caecum were measured. Plasma glucagon-like peptide-2 (GLP-2) concentration and GLP-2 receptor (GLP-2R) mRNA levels in the epithelium were also determined. RESULTS: Pectin supplementation resulted in significant increases in the length, weight, and number of Ki-67-positive cells in the ileum, caecum and colon. Although pectin supplementation did not affect the caecal microbial flora that produced SCFAs, the caecal SCFA content was significantly increased. Pectin supplementation also induced an increase in the plasma GLP-2 concentration, but did not affect the GLP-2R mRNA levels in the small intestine. CONCLUSIONS: The increases in the caecal SCFAs and plasma GLP-2 levels induced by pectin supplementation may cause mucosal proliferation in the lower intestinal tract.
Animals↗