Seong-Joon Koh

Anti-inflammatory mechanism of metformin and its effects in intestinal inflammation and colitis-associated colon cancer.

The aim of this study is to evaluate the effect of metformin on intestinal inflammation.

Fluoxetine inhibits NF-κB signaling in intestinal epithelial cells, and ameliorates experimental colitis and colitis-associated colon cancer in mice

Although fluoxetine, a selective serotonin reuptake inhibitor, is known to demonstrate anti-inflammatory activity, little information is available on the effect of fluoxetine regarding intestinal inflammation. This study investigates the role of fluoxetine in the attenuation of acute murine colitis by suppression of the NF-κB pathway in intestinal epithelial cells (IEC). Fluoxetine significantly inhibited activated NF-κB signals and the upregulated expression of interleukin-8 (IL-8) in COLO 205 colon epithelial cells stimulated with tumor necrosis factor-α (TNF-α). Pretreatment with fluoxetine attenuated the increased IκB kinase (IKK) and IκBα phosphorylation induced by TNF-α. In a murine model, administration of fluoxetine significantly reduced the severity of dextran sulfate sodium (DSS)-induced colitis, as assessed by the disease activity index, colon length, and histology. In addition, the DSS-induced phospho-IKK activation, myeloperoxidase activity, a parameter of neutrophil accumulation, and the secretion of macrophage-inflammatory protein-2, a mouse homolog of IL-8, were significantly decreased in fluoxetine-pretreated mice. Moreover, fluoxetine significantly attenuated the development of colon cancer in mice inoculated with azoxymethane and DSS. These results indicate that fluoxetine inhibits NF-κB activation in IEC and that it ameliorates DSS-induced acute murine colitis and colitis-associated tumorigenesis, suggesting that fluoxetine is a potential therapeutic agent for the treatment of inflammatory bowel disease.

Mortality associated with proton pump inhibitors in cirrhotic patients with spontaneous bacterial peritonitis

The aims of this study were to investigate whether acid suppressive therapy increases the risk of spontaneous bacterial peritonitis (SBP) and to define factors associated with mortality in cirrhotic patients with SBP.

Psychosocial Stress in Nurses With Shift Work Schedule Is Associated With Functional Gastrointestinal Disorders

Background/Aims The aim of this study was to investigate the role of psychosocial problems and their associations with rotating shift work in the development of functional gastrointestinal disorders. Methods In this cross-sectional observation study, survey was administered to nurses and nurse assistants in a referral hospital. In addition to demographic questions, subjects were asked to complete the Rome III Questionnaire, Pittsburgh Sleep Quality Index and Rome III Psychosocial Alarm Questionnaire. Results Responses from 301 subjects were assessed. The overall prevalence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) were 15.0% and 19.6%, respectively. Psychosocial alarms were prevalent in the nursing personnel (74.8% with alarm presence and 23.3% with serious condition) and were more frequent among rotating shift workers (84.7% vs. 74.5% for alarm presence and 28.1% vs. 13.3% for serious condition). The prevalence of both IBS and FD significantly increased with psychosocial risk. An independent risk factor for IBS was serious psychosocial alarm (adjusted odds ratio [aOR], 10.75; 95% confidence interval (CI), 1.30–88.99; P = 0.028). Serious psychosocial alarm was an independent risk factor for FD (aOR, 7.84; 95% CI, 1.98–31.02; P = 0.003). Marriage (aOR 0.30; 95% CI, 0.09–0.93; P = 0.037) was associated with the decreased risk of FD. Conclusions The high prevalence of psychosocial stress among nurses who work rotating shifts is associated with the development of functional gastrointestinal disorders.

Circulating ghrelin levels and obestatin/ghrelin ratio as a marker of activity in ulcerative colitis.

Background/Aims Ghrelin levels are known to increase in patients with ulcerative colitis (UC), but serum obestatin levels in UC patients are not well elucidated. The aim of this study was to examine the relationship between serum ghrelin and obestatin levels and disease activity in UC patients. Methods The serum ghrelin and obestatin levels were measured in 21 UC patients (12 with active disease and 9 in remission) using enzyme-linked immunosorbent assay. The relationship between the circulating levels of these 2 hormones and disease activity was analyzed. The colonic mucosal mRNA expression of ghrelin and obestatin was measured by quantitative reverse transcription polymerase chain reaction. Results The mean serum ghrelin values were significantly higher in patients with active disease than in patients with remission (1370.6±404.3 vs. 783.5±235.3 pg/mL, P=0.001). Colonic mucosal mRNA expression of ghrelin was also significantly higher in patients with active disease than in patients in remission (0.805±0.214 vs. 0.481±0.356, P=0.018). However, the mean serum obestatin levels and colonic mucosal mRNA expression of obestatin were not significantly different between both groups. The circulating obestatin/ghrelin ratio was significantly lower in patients with active UC than in patients in remission (0.32±0.08 vs. 0.58±0.20, P=0.001). Conclusions The serum ghrelin levels and the obestatin/ghrelin ratio were related to the activity of UC, but serum obestatin was not related to activity of UC. The ghrelin levels and the obestatin/ghrelin ratio could serve as activity markers in patients with UC.

The guggulsterone derivative GG-52 inhibits NF-κB signaling in bone marrow-derived dendritic cells and attenuates colitis in IL-10 knockout mice.

AIMS We previously demonstrated that the novel guggulsterone derivative guggulsterone-52 (GG-52) inhibited the activation of nuclear factor (NF)-κB signaling in intestinal epithelial cells and had preventive and therapeutic effects on dextran sulfate sodium-induced acute colitis. This study investigates the anti-inflammatory effects of GG-52 on bone marrow-derived dendritic cells (BMDCs) and chronic colitis in IL-10(-/-) mice. MAIN METHODS BMDCs were generated from the femurs of C57BL/6 wild-type and IL-10(-/-) mice. BMDCs were stimulated with lipopolysaccharide (LPS) in the presence or absence of GG-52. The effect of GG-52 on NF-κB signaling in BMDCs was examined by real-time RT-PCR for IL-12p40 and TNF-α gene expression, western blotting for IκBα degradation, and electrophoretic mobility shift assay. For in vivo studies, wild-type or IL-10(-/-) mice were treated with or without GG-52. Colitis was quantified by the evaluation of histopathological findings. Double immunofluorescence staining for CD11c and phosphorylated IκB kinase (IKK)-α was performed to detect IKK activation in DCs in colonic tissue. KEY FINDINGS GG-52 significantly inhibited LPS-induced IL-12p40 and TNF-α gene expression, IκBα degradation, and NF-κB DNA binding activity in BMDCs. In the IL-10(-/-) mouse model chronic colitis, administration of GG-52 significantly reduced the severity of colitis as assessed by histopathology, and suppressed IKK activation in DCs in colonic tissue. SIGNIFICANCE These results indicate that the novel guggulsterone derivative GG-52 blocks NF-κB activation in BMDCs and ameliorates chronic colitis in IL-10(-/-) mice, which suggest that GG-52 is a potential therapeutic agent for inflammatory bowel diseases.

Clinical and endoscopic characteristics of drug-induced esophagitis

AIM To investigate clinical, endoscopic and pathological characteristics of drug-induced esophagitis. METHODS Data for patients diagnosed with drug-induced esophagitis from April 2002 to May 2013 was reviewed. Patients diagnosed with malignancy, viral or fungal esophagitis were excluded. Clinical, endoscopic and pathological characteristics of patients diagnosed with drug-induced esophagitis were analyzed. RESULTS Seventy-eight patients were diagnosed with drug-induced esophagitis. Their mean age was 43.9 ± 18.9 years and 35.9% were male. Common symptoms were chest pain (71.8%), odynophagia (38.5%) and dysphagia (29.5%). The endoscopic location was in the middle third of esophagus in 78.2%. Endoscopic findings were ulcer (82.1%), erosion (17.9%), ulcer with bleeding (24.4%), coating with drug material (5.1%), impacted pill fragments (3.8%) and stricture (2.6%). Kissing ulcers were observed in 43.6%. The main causative agents were antibiotics and non-steroidal anti-inflammatory drugs. All the patients were treated with proton pump inhibitors (PPIs) or sucralfate, and the causative drugs were discontinued. Nineteen patients with drug-induced esophagitis were followed up with endoscopy and revealed normal findings, scars or healing ulcers. CONCLUSION Drug-induced esophagitis mainly presents as chest pain, odynophagia and dysphagia, and may be successfully treated with PPIs and discontinuation of the causative drug. Kissing ulcers were observed in 43.6%.

Fexofenadine Regulates Nuclear Factor-κB Signaling and Endoplasmic Reticulum Stress in Intestinal Epithelial Cells and Ameliorates Acute and Chronic Colitis in Mice

The aim of this study was to evaluate the effect of fexofenadine on intestinal inflammation. HCT116 and COLO205 cells were pretreated with fexofenadine and then stimulated with tumor necrosis factor (TNF)-α. Interleukin (IL)-8 expression was determined by real-time reverse-transcription polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. DNA-binding activity of nuclear factor-κB was assessed by electrophoretic mobility shift assay. The molecular markers of endoplasmic reticulum (ER) stress were evaluated by Western blot analysis and PCR. In the acute colitis model, mice were given 4% dextran sulfate sodium (DSS) for 5 days with or without fexofenadine. IL-10−/− mice were used to evaluate the effect of fexofenadine on chronic colitis. Fexofenadine significantly inhibited the upregulated expression of IL-8 in HCT116 and COLO205 cells stimulated with TNF-α. Fexofenadine suppressed nuclear factor-κB DNA-binding activity. C/EBP homologous protein mRNA expression was enhanced in the presence of TNF-α, and it was dampened by pretreatment of fexofenadine. In addition, the induction of ER stress markers caspase-12 and p-eukaryotic initiation factor 2 (eIF2)-α was significantly suppressed by the pretreatment of fexofenadine. Administration of fexofenadine significantly reduced the severity of DSS-induced murine colitis, as assessed by the disease activity index, colon length, and histology. In addition, the DSS-induced phospho-IκB kinase activation was significantly decreased in fexofenadine-pretreated mice. Finally, fexofenadine significantly reduced the severity of colitis and the immunoreactivity of caspase-12 and p-eIF2-α in IL-10−/− mice as compared with controls. These results suggest that fexofenadine is a potential therapeutic agent for the treatment of inflammatory bowel disease.

Psoriasis concurrent with inflammatory bowel disease

Previous studies have indicated an association between psoriasis and inflammatory bowel disease (IBD), and the concurrence of the two diseases reportedly has higher morbidities in Caucasian populations. However, reports on the concurrence of psoriasis with IBD in the Asian population in the literature are scarce.

Matricellular Protein Periostin Mediates Intestinal Inflammation through the Activation of Nuclear Factor κB Signaling

Periostin is a matricellular protein that interacts with various integrin molecules on the cell surface. Although periostin is expressed in inflamed colonic mucosa, its role in the regulation of intestinal inflammation remains unclear. We investigated the role of periostin in intestinal inflammation using Postn-deficient (Postn-/-) mice. Intestinal epithelial cells (IECs) were transfected by Postn small interfering RNAs. Periostin expression was determined in colon tissue samples from ulcerative colitis (UC) patients. Oral administration of dextran sulfate sodium (DSS) or rectal administration of trinitrobenzene sulfonic acid, induced severe colitis in wild-type mice, but not in Postn-/- mice. Administration of recombinant periostin induced colitis in Postn-/- mice. The periostin neutralizing-antibody ameliorated the severity of colitis in DSS-treated wild-type mice. Silencing of Postn inhibited inteleukin (IL)-8 mRNA expression and NF-κB DNA-binding activity in IECs. Tumor necrosis factor (TNF)-α upregulated mRNA expression of Postn in IECs, and recombinant periostin strongly enhanced IL-8 expression in combination with TNF-α, which was suppressed by an antibody against integrin αv (CD51). Periostin and CD51 were expressed at significantly higher levels in UC patients than in controls. Periostin mediates intestinal inflammation through the activation of NF-κB signaling, which suggests that periostin is a potential therapeutic target for inflammatory bowel disease.