Imiquimod-induced CCR9 Ameliorates murine TNBS Colitis.

AIMS: To investigate whether Imiquimod (IMQ) as TLR7 ligand protects mice from colonic inflammation and the mechanisms underlying in such immunoregulatory conditions.　METHODS: Murine colitis was induced to Balb/c mice by administration of trinitrobenzene sulfonic acid (TNBS) with or without daily intraperitoneal administration of IMQ.　Colitis was evaluated by body weight decreases and by histological score.　Also colonic mRNA expression was measured by RT-PCR.　To confirm the induction of Regulatory T cells (Tregs) by type-1 IFN from pDCs, we generated mouse bone marrow-derived pDCs and co-cultured these with CD4+ T cells isolated from mouse spleen with or without IMQ stimulation.　Cytokine production in the culture supernatant was measured by ELISA and the number of Tregs were analyzed by flow cytometry.　Spleen and mesenteric lymph nodes (MLN) from IMQ-treated mice were collected, and mRNA expressions of cytokine were measured by RT-PCR and cytokine productions were measured by ELISA.　Tregs and chemokine expressions were analyzed in colon of TNBS-induced colitis mouse by immunohistochemistry.　RESULTS: Administration of IMQ significantly suppressed colonic inflammation of TNBS-induced colitis.　In the colons of IMQ-treated mice, mRNA expression of TNF-α was decreased, and strong expressions of IL-6, IFN-ß and TGF-ß were detected.　IL-10 and TGF-ß productions were increased in the supernatant of co-cultured cells stimulated with IMQ, although we were unable to detect Treg differentiaton in IMQ-stimulated co-cultured cells.　In MLN of IMQ-treated mice, strong expressions of TLR7, IFN-ß, TGF-ß and Foxp3 mRNA were detected.　IL-10 production from MLN cells was also increased in the IMQ-treated group.　Finally, Tregs in the inflamed colon and CCR9 in MLN of IMQ-treated mice were detected.　CONCLUSION: These results suggest that IMQ protects mice from TNBS colitis through induction of CCR9, which regulates accumulation of Tregs in the inflamed colon.

[Outcomes of Bridge to Surgery for Obstructive Colorectal Cancer after Metallic Stent Placement in Our Hospital].

Recently, the endoscopic placement of self-expanding metallicstents (SEMSs)has become widespread for the treatment of acute malignant colorectal obstruction. This study was designed to evaluate the clinical outcomes of 22 patients with obstructive colorectal cancer who underwent SEMS placement as a bridge to surgery(BTS)from January 2012 to December 2015. The subjects comprised 15 men and 7 women with a mean age of 68.1 years. Placement and decompression were successfully achieved in all cases. No serious complications arose from the placement. After excluding 3 patients for whom preoperative chemotherapy or treatment for another disease was prioritized, the mean interval to surgery for the remaining 19 patients was 18.2 days. Operative anastomosis was performed in all patients except those who had tandem lesions. Although postoperative complications including minor leakage(n=1), surgical site infection(n=1), and ileus(n=1)were observed, the course was effective in most patients. Bridge to surgery is a relatively easy, safe, and effective method for the treatment of obstructive colorectal cancer that enables preoperative intestinal decompression and one-stage resection, preventing stoma creation.

Concurrent primary sclerosing cholangitis and eosinophilic colitis.

A 39-year-old man presented with diarrhea and abdominal pain. At 26 years of age, he was found to have eosinophilia and abnormal liver function parameters, for which prednisolone therapy was started. He subsequently underwent a liver biopsy and endoscopic retrograde cholangiopancreatography, and received a diagnosis of primary sclerosing cholangitis (PSC). On presentation to our hospital, he was further diagnosed with eosinophilic colitis based on aggravation of diarrhea and severe eosinophilic infiltration in the colonic mucosa. We herein report a rare case of concurrent PSC and eosinophilic colitis.

Modulating Toll-like receptor 4 signaling pathway protects mice from experimental colitis.

BACKGROUND/AIM: Several reports have indicated that environmental factors and defects in innate immunity are central to the pathogenesis of inflammatory bowel disease (IBD). Although bacteria producing lipopolysaccharide (LPS), which is a Toll-like receptor (TLR) 4 agonist, play a crucial role in the development of experimental colitis, LPS tolerance following initial exposure to LPS can result in a state of hyporesponsiveness to subsequent LPS challenge. Therefore, we initiated this study to explore the role of LPS tolerance in the development of colitis. METHODS: Dextran sulfate sodium (DSS) colitis was induced in Balb/c mice with or without daily intraperitoneal administration of LPS. Disease activity and cytokine mRNA expression in the colon were evaluated. To confirm LPS tolerance, mouse conventional bone marrow-derived dendritic cells (BMDC) were preincubated with or without LPS, and were restimulated with LPS 24 h after first exposure. Cytokine production was measured by ELISA, and mRNA expression was evaluated by RT-PCR. Furthermore, we investigated the expression of negative regulators of LPS tolerance in BMDC. RESULTS: Administration of LPS significantly suppressed colonic inflammation of DSS-induced colitis. After subsequent stimulation with LPS, TNF-α production was reduced in BMDC. IRAK-M, a negative regulator of TLR4 signaling, mRNA expression was up-regulated in LPS-treated BMDC. CONCLUSION: LPS tolerance was able to protect mice from DSS-induced colitis, and IRAK-M participated in this tolerance. Taken together, these observations suggest that loss of exposure to LPS is involved in the pathogenesis of IBD.

A case of emphysematous pyelonephritis in a patient with rheumatoid arthritis taking corticosteroid and low-dose methotrexate.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that is characterized by chronic synovial inflammation. Patients with RA have increased risk of infection; this is related to RA itself or the adverse effects of medication. In this report, we describe a case of emphysematous pyelonephritis in a patient with RA associated with AA amyloidosis and steroid-induced diabetes mellitus who was taking corticosteroid and low-dose methotrexate.