Clinical Background Factors as Predictors of the Efficacy of 5-Aminosalicylic Acid Suppositories in Patients with Ulcerative Colitis.

Introduction: Although the efficacy of 5-aminosalicylic acid (ASA) suppositories for ulcerative colitis (UC) has been reported in many studies, many studies have also described poor adherence to 5-ASA suppository regimens. We aimed to identify the clinical background factors that influence adherence to 5-ASA suppositories to improve adherence and efficacy of the treatment. Methods: We conducted a retrospective cohort study of 61 patients with active UC who were using 5-ASA suppositories. All patients underwent endoscopy and rectal biopsy for histological diagnosis prior to 5-ASA suppository treatment. The efficacy of 5-ASA suppository treatment was compared in relation to clinical background factors (sex, age, disease duration, disease type, clinical activity, Ulcerative Colitis Endoscopic Index of Severity, histological activity, serum C-reactive protein level, concomitant use of immunomodulators, history of steroid use, and dose of oral 5-ASA). Results: The efficacy of 5-ASA suppositories was significantly related to low Lichtiger Colitis Activity Index (LCAI) scores and proctitis type prior to its use. In terms of sex, females tended to show higher efficacy. Multivariate logistic regression analysis using these three factors showed high predictive value for the efficacy of 5-ASA suppositories (AUC, 0.788; sensitivity, 87.2%; and specificity, 63.7%). Conclusion: This study is the first to extract clinical background factors for predicting the efficacy of 5-ASA suppositories. The use of 5-ASA suppositories in patients who are expected to show efficacy will be effective in improving patient co-operation.

Mucosal Addressin Cell Adhesion Molecule 1 Expression Reflects Mucosal Inflammation and Subsequent Relapse in Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: Mucosal addressin cell adhesion molecule 1 [MAdCAM-1] is upregulated in the vascular endothelium of the colonic mucosa in ulcerative colitis [UC]. Although the association between MAdCAM-1 expression and mucosal inflammation has been discussed, the association with the clinical course of UC patients has not been reported. In this study we investigated not only the association between mucosal MAdCAM-1 expression and mucosal inflammation, but also its association with subsequent relapse in UC patients with clinical remission. METHODS: Eighty UC patients in remission who visited Kyoto Prefectural University of Medicine for follow-up for 2 years were included. Biopsy samples were collected during colonoscopy, and transcriptional expression levels of UC-related cytokines and MAdCAM-1 were quantified using real-time polymerase chain reaction. MAdCAM-1 mRNA expression and protein expression by immunohistochemistry were compared in patients who subsequently relapsed and those who remained in remission and were examined in relation to endoscopic findings, histological activity and cytokine expression. RESULTS: MAdCAM-1 expression was correlated with endoscopic severity, and significantly elevated in histologically active mucosa than inactive mucosa. Furthermore, MAdCAM-1 expression levels were closely correlated with those of several cytokines. MAdCAM-1 mRNA and protein expression were significantly higher in the relapse group than in the remission group, indicating that MAdCAM-1 expression in the mucosa is already elevated in UC patients in clinical remission who subsequently relapse. CONCLUSIONS: MAdCAM-1 expression in the colonic mucosa of UC patients is related to mucosal inflammation and subsequent relapse; it may serve as a marker for both relapse and therapeutic effectiveness in UC.

Retrospective investigation of mesalamine intolerance in patients with ulcerative colitis.

Mesalamine is a key drug in the treatment of ulcerative colitis (UC) for both induction and maintenance therapy. On the other hand, it is known that there are some cases of mesalamine intolerance that are difficult to distinguish from symptoms due to aggravation of UC. The aim of this study is to investigate the clinical characteristic of mesalamine intolerance in UC. A retrospective, observational study was conducted. We enrolled 31 patients who were diagnosed as mesalamine intolerance between April 2015 to March 2020. We examined clinical features, time to onset, drug types of mesalamine, DLST positive rate, colonoscopy findings, disease activity, and clinical course after diagnosis. The average dose of mesalamine was 3.69 g and DLST-positive was 57.1%. Within the first 2 weeks from the start of mesalamine, 51.6% showed symptoms of intolerance. The serum CRP level was relatively high at ≥10.0 mg/dl in 53.6% of the cases. There was no difference in clinical background, symptoms, or laboratory findings between patients with DLST-positive and negative. In this study, we clarified the clinical characteristics of mesalamine intolerant patients, and found no difference in the clinical background or success rate of desensitization therapy between positive and negative DLST cases.

Investigation on the Inhibitory Effect of Wnt-5a on Colonic Mucosal Inflammation in Patients with Ulcerative Colitis.

BACKGROUND: Recent progress in ulcerative colitis (UC) treatment has been remarkable, and various medications have been applied. However, some patients with UC are refractory to treatment and convert to surgery. AIM: To investigate the role of colonic mucosal Wnt-5a expression in the pathogenesis of UC and the effect of bioactive Wnt-5a peptide on colitis in mice. METHODS: Wnt-5a peptide was intraperitoneally administered to mice every day from the beginning of dextran sulfate sodium (DSS) treatment. The severity of colitis was evaluated based on body weight change, colonic length, and histological scores. Colonic mucosal TNF-α and KC mRNA expression levels were measured. This study included 70 patients with UC in clinical remission. Wnt-5a, TNFα, and IL-8 mRNA expression in the rectal mucosa were measured by quantitative real-time polymerase chain reaction using biopsy materials. Wnt-5a mRNA expression levels were compared between patients who relapsed and those in remission. We examined the correlation of Wnt-5a expression with TNF-α and IL-8 expression. RESULTS: Wnt-5a peptide significantly attenuated the severity of DSS-induced colitis. Moreover, mucosal TNF-α and KC mRNA expression were significantly suppressed by Wnt-5a peptide treatment. Wnt-5a mRNA levels were significantly lower in patients with subsequent relapse than in those who remained in remission. Mucosal Wnt-5a was inversely correlated with TNF α and IL-8 expression. CONCLUSION: Wnt-5a peptide suppressed colitis in mice, and decreased Wnt-5a expression was strongly associated with relapse in patients with UC. Wnt-5a may have an inhibitory effect on mucosal inflammation in UC, and Wnt-5a peptide could be a new therapeutic strategy.

Mucosal interleukin-8 expression as a predictor of subsequent relapse in ulcerative colitis patients with Mayo endoscopic subscore 0.

BACKGROUND AND AIM: Complete endoscopic mucosal healing is defined as a Mayo endoscopic subscore of 0. Some patients diagnosed with a Mayo endoscopic subscore 0 may present with subsequent clinical relapse. Here, we aimed to demonstrate mucosal cytokine profile as a predictor of clinical relapse in ulcerative colitis patients with a Mayo endoscopic subscore of 0 as a marker of mucosal healing. METHODS: We conducted prospective observational pilot study to examine the relationship between mucosal cytokine expression and subsequent relapse of UC patients diagnosed with a Mayo endoscopic subscore of 0. We enrolled 55 patients, and expression of cytokines tumor necrosis factor-α, interferon γ, interleukin-1ß, interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-7, interleukin-8, interleukin-9, interleukin-10, interleukin-12, interleukin-13, interleukin-15, interleukin-17A, interleukin-17F, interleukin-18, interleukin-21, interleukin-22, interleukin-23, interleukin-27, and interleukin-33 was measured by quantitative real-time PCR using rectal mucosa biopsy materials. Cytokine expression levels were compared between patients who relapsed between March 1, 2016, and March 30, 2020, of the study period and those who remained in remission. RESULTS: Ten cytokines, including interleukin-2, interleukin-4, interleukin-8, interleukin-10, interleukin-12, interleukin-15, interleukin-17A, interleukin-21, interleukin-23, and interleukin-33, were significantly elevated in patients with subsequent relapse compared with those who remained in remission. Interleukin-8 expression was the most useful predictor. CONCLUSIONS: In the rectal mucosa of ulcerative colitis patients with Mayo endoscopic subscore 0, levels of several cytokines were elevated in cases of subsequent relapse. Among these, interleukin-8 expression was the most useful for predicting relapse.

[Voluntary inoculation of hepatitis B vaccine at pediatric medical institutions].

We conducted a questionnaire survey on voluntary inoculation of hepatitis B (HB) vaccine to children at 79 pediatric clinics. The voluntary vaccination rate was 65.2%, the desired vaccination target was "all infants" at 84.8% of clinics, the recommended method was "only when the patient wishes" at a rate of 80.0%, and "actively recommended" at 20.0%. If there was a request, 71.7% of clinics answered that they would like to recommend it in the future, and 38.9% said that it was difficult to recommend it because of the voluntary nature of vaccination. The requests were "expansion of the scope of regular vaccination" at 60.9% of clinics and "enlightenment activities and information provision" at 54.3%. Since it was suggested that voluntary vaccination is difficult to recommend, it is necessary to proactively provide information and public relations activities regarding its necessity to medical personnel and parents.

The efficacy of linked color imaging for the endoscopic diagnosis of mucosal healing in quiescent ulcerative colitis.

BACKGROUND AND AIM: The Mayo Endoscopic Subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) are used to assess endoscopic mucosal healing in patients suffering from ulcerative colitis. Although mucosal healing is defined by MES 0, relapse of ulcerative colitis is often observed. Over a 48-month period, this study investigated the efficacy of linked color imaging (LCI) in predicting the long-term prognosis of ulcerative colitis patients diagnosed with MES 0. METHODS: Overall, 26 patients in ulcerative colitis remission, diagnosed with MES 0, were enrolled. Using a LASEREO endoscopic system (Fujifilm Co., Tokyo, Japan), endoscopic colonic images were assessed with linked color imaging and the colitis endoscopic index of severity. Endoscopic LCI images were separated into three subgroups (A, no redness; B, redness with visible vessels; and C, redness without visible vessels). The Geboes score was used to evaluate histology; active mucosa was defined as GS > 2B.1. RESULTS: Linked color imaging classification subdivided colonic mucosa, which had been diagnosed with MES 0, into two classes. The LCI-A group did not relapse, and the non-relapse rate was significantly higher (P = 0.018) than that in the LCI-B group. No difference in relapse rates was observed between patients with a colitis endoscopic index of severity of 0 and 1 (P = 0.655). There was no statistical difference between the composition of LCI-A group and the relapse rate between active and inactive mucosa diagnosed by Geboes score. CONCLUSIONS: This methodology can be used to evaluate mucosal healing and predict long-term outcomes in ulcerative colitis patients.

Low serum albumin at admission is a predictor of early colectomy in patients with moderate to severe ulcerative colitis.

BACKGROUND AND AIM: Several studies have identified postinduction therapy predictors of long-term outcomes of ulcerative colitis (UC) in patients who experienced the first attack of the disease or relapsed after therapy. We aimed to identify the preinduction therapy predictors at admission that predicted early colectomy in patients with moderate to severe UC. METHODS: Ninety-five patients with moderate to severe UC who underwent induction therapy at the Kyoto Prefectural University of Medicine hospital between August 2008 and March 2020 were retrospectively included and categorized into two groups: the colectomy group (n = 27) and the noncolectomy group (n = 68). The clinical parameters (age, gender, disease extent, and disease activity on admission), induction therapies administered [including 5-aminosalicylic acid, steroids, immunomodulators, calcineurin inhibitor, and anti-Tumor Necrosis Factor (TNF)-α antibodies], and laboratory data (hemoglobin, albumin, C-reactive protein, and cytomegalovirus reactivation on admission) were evaluated and compared between the two groups. Multivariate logistic regression analyses were performed to identify significant predictors of early colectomy, and P < 0.05 was considered significant. RESULTS: All clinical parameters were not significant predictors of colectomy. Among laboratory parameters, the serum albumin level on admission was a significant independent predictor of colectomy (odds ratio: 6.097, 95% confidence interval: 1.8310-20.3047). Receiver operating characteristic curves were plotted for the serum albumin levels of the 95 patients at admission. The cut-off value of serum albumin was 2.45 g/dL. CONCLUSIONS: When the serum albumin level of UC patients at admission is below 2.45 g/dL, we should consider presenting the option of surgical treatment to patients.

Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis.

BACKGROUND: The role of IL-12/23 in the pathogenesis of ulcerative colitis (UC) is unclear. We analyzed mucosal IL-12/23 expression and its relationship with endoscopic severity, histological activity, and UC relapse. METHODS: Rectal biopsies were collected from 70 UC patients with clinical remission. IL-12, IL-23, IFN-γ, IL-17A, and IL-17F mRNA expression was measured by real-time PCR. Endoscopic severity and histological activity were evaluated using the Mayo endoscopic subscore (MES) and the Geboes score, respectively. RESULTS: The longest follow-up period was 51 months. Thirty-four patients relapsed during the study period. Samples from these subsequently relapsed patients formed the "relapse" group, while those from patients that did not relapse formed the "remission" group. IL-12 (P = 0.0003) and IL-23 (P = 0.014) mRNA expression was significantly higher in the relapse than the remission group. Expression of IL-23 (P = 0.015) but not IL-12 (P = 0.374) was correlated with MES. However, in patients with an MES of 0 and 1, IL-12 expression was statistically higher in the relapse than the remission group (P = 0.0015, P = 0.0342). IL-12 and IL-23 expression did not vary significantly between histologically active and inactive mucosa; both were higher in histologically inactive patients in the remission group (IL-12: P = 0.0002, IL-23: P = 0.046). CONCLUSIONS: Rectal IL-12 and IL-23 expression was elevated in the relapse group, but IL-12 was more strongly associated with UC relapse, irrespective of endoscopic severity and histological activity. Mucosal IL-12 was elevated in patients with deep mucosal healing. Our results suggest an important role of IL-12 in UC pathogenesis and the molecular mechanism of UC relapse.

[Questionnaire survey on hepatitis B vaccine in clinics].

We conducted a questionnaire survey on the status of implementation of hepatitis B vaccination and HBs antibody testing. It involved medical personnel covering 484 regional medical institutions in the Osaka Province. Results showed that the recognition rate was 30.1%, the hepatitis B vaccination implementation rate was 38.9%, and that of HBs antibody testing was 38.9%. Although 42.5% of the medical institutions had experienced needle-stick injuries, some medical institutions did not respond properly. The low implementation rate of hepatitis B vaccination and HBs antibody test could be explained by lack of recognition for hepatitis B infection control guidelines. Therefore, we can achieve a possible improvement in the control of infection in the Province, if sensitization programs on hepatitis B infection control are organized in the various regional medical institutions in order to provide adequate information and raise awareness on the importance of respecting these guidelines.

[The effect of introducing an on-call system for attending physicians].

Gastroenterologists working in hospitals that have adopted the chief physician system are often required to work overtime during the night and on holidays treating critically ill patients and ordering emergency tests. To help alleviate the attending physician's duties, our hospital initiated an on-call system in October 2019 to replace the existing system. Changes in overtime hours worked and business stress before and after the introduction of the on-call system were verified. After the introduction of the on-call system, both overtime hours and the number of holidays worked decreased and work stress was reduced. We report that the on-call system is a suitable alternative to the attending physician system because it increases the work efficiency and satisfaction of attending physicians.

Familial Mediterranean Fever without Fever.

Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease commonly observed around the Mediterranean basin presenting as recurrent febrile episodes. We herein describe a Japanese case of genetically-confirmed FMF, in which fever was lacking during attacks. An otherwise healthy 34-year-old man presented with frequent episodes of abdominal pain, which resolved spontaneously. During the attacks, the patient was afebrile, but the inflammatory marker levels in his blood were increased. Abdominal CT demonstrated enhancement of the jejunal membrane. After the initiation of colchicine therapy, the patient experienced no attacks for more than one year. The diagnosis of FMF was confirmed by a genetic analysis.

[Early onset of metronidazole-induced peripheral neuropathy in a patient with amoebic colitis:a case report].

Peripheral neuropathy reportedly develops after a long period of metronidazole administration. Here, we report a case of amoebic colitis in which peripheral neuropathy occurred approximately 24 hours after administering metronidazole. A 76-year-old man presented with mucous and bloody stool. Initially, lower gastrointestinal endoscopy and stool analysis confirmed the occurrence of amoebic colitis, and metronidazole was then intravenously administered. The following day, however, the patient experienced a diminished sensation in a glove-and-stocking distribution in his extremities, followed by bilateral burning foot pain. After the withdrawal of metronidazole, the symptoms improved and finally disappeared 3 months later.

[Long-Term Survival of a Patient with Small Cell Esophageal Carcinoma Who Underwent Multidisciplinary Therapy-ACase Report].

The patient was a 69-year-old woman.Upper gastrointestinal endoscopy showed a protruding tumor in the mid-thoracic esophagus, and biopsy revealed small cell carcinoma in November 2012. Four courses of neoadjuvant chemotherapy comprising CDDP and CPT-11 were administered, and radical resection was performed in March 2013.I n March 2014, chest computed tomography revealed the recurrence of mediastinal lymph nodes; thus, we administered chemoradiotherapy comprising 5- FU and CDDP, and the size of the recurrent tumors decreased.However, in February 2015, positron emission tomographycomputed tomography revealed liver metastases.Therefore, we switched to a new chemotherapy regimen containing CDDP and VP-16.Although the treatment was very effective and the liver metastases significantly decreased in size, it was discontinued after 9 courses owing to neurotoxicity.Next, 7 courses of chemotherapy comprising amrubicin, which is administered for treating small cell lung carcinoma, were administered, which suppressed tumor growth for approximately 8 months.However, the tumor then re-grew.Chemotherapy comprising S-1 was administered; however, the tumor gradually progressed.The patient died 51 months after the initial treatment.

Ginsenoside Rb1 promotes intestinal epithelial wound healing through extracellular signal-regulated kinase and Rho signaling.

BACKGROUND AND AIM: Daikenchuto, a traditional Japanese herbal medicine, has been reported to exhibit anti-inflammatory effects against intestinal inflammation. However, whether daikenchuto has a therapeutic effect against intestinal mucosal injuries remains unclear. Thus, the aim of this study was to determine the effect of daikenchuto on intestinal mucosal healing. METHODS: Colitis was induced in male Wistar rats by using trinitrobenzenesulfonic acid. Daikenchuto (900 mg/kg/day) was administered for 7 days after the induction of colitis. Thereafter, intestinal mucosal injuries were evaluated by determining the colonic epithelial regeneration ratio ([area of epithelial regeneration/area of ulcer] × 100). Restoration of rat intestinal epithelial cells treated with daikenchuto and its constituent herbs (Zanthoxylum fruit, processed ginger, and ginseng) and ginsenoside Rb1, which is a ginseng ingredient, was evaluated using a wound-healing assay. RESULTS: The colon epithelial regeneration ratio in the daikenchuto-treated rats was significantly higher than that in the control rats. Daikenchuto, ginseng, and ginsenoside Rb1 enhanced wound healing, and the ginsenoside Rb1-induced enhancement was inhibited by extracellular signal-regulated kinase and Rho inhibitors. CONCLUSIONS: Daikenchuto and its constituent, ginsenoside Rb1, promoted wound healing. Because mucosal healing is one of the most important therapeutic targets in patients with inflammatory bowel disease, ginsenoside Rb1 may be a novel therapeutic agent against intestinal mucosal damage such as that occurring in intestinal bowel disease.

Elevated ER stress exacerbates dextran sulfate sodium-induced colitis in PRDX4-knockout mice.

BACKGROUND AND AIMS: Peroxiredoxin 4 (PRDX4), a secretory protein that is preferentially retained in the endoplasmic reticulum (ER), is encoded by a gene located on the X chromosome and highly expressed in colonic tissue. In this study, we investigated the role of PRDX4 by means of male PRDX4-knockout (PRDX4-/y) mice in the development of intestinal inflammation using a dextran sulfate sodium (DSS)-induced colitis model. MATERIALS AND METHODS: Acute colitis was induced with DSS (2.5% in drinking water) in wild-type (WT) and PRDX4-/y male C57BL/6 mice. Histological and biochemical analyses were performed on the colonic tissues. RESULTS: PRDX4 was mainly localized in the colonic epithelial cells in WT mice. The disease activity index (DAI) scores of PRDX4-/y mice were significantly higher compared to those of WT mice. Specifically, PRDX4-/y mice showed marked body weight loss and shortening of colon length compared to WT mice, whereas the myeloperoxidase levels were increased in PRDX4-/y compared to WT mice. In addition, the mRNA expression levels of TNF-α and IFN-γ were significantly higher in the colonic mucosa of PRDX4-/y compared to WT mice. Moreover, the levels of CHOP and activated caspase 3 were higher in the colonic tissues of PRDX4-/y compared to WT mice following treatment with DSS. The ER also showed greater expansion in PRDX4-/y than WT mice, which was consistent with severe ER stress under PRDX4 deficiency. CONCLUSION: Our results demonstrated that the lack of PRDX4 aggravated the colonic mucosal damage induced by DSS. Because PRDX4 functions as an ER thiol oxidase as well as an antioxidant, DSS induced oxidative damage and ER stress to a greater degree in PRDX4-/y than WT mice. These findings suggest that PRDX4 may represent a novel therapeutic molecule in intestinal inflammation.

[A case of cholangiolocellular carcinoma found to be hepatic hemangioma at 16-month follow up].

We report a rare case of hepatic cholangiolocellular carcinoma (CoCC) with long-term observation. A 73-year-old woman was found to have a solitary hepatic tumor with a diameter of 10mm on dynamic computed tomography (CT), which showed peripheral enhancement in the arterial phase and enhancement retention in the delayed phase. Although it was initially diagnosed as hepatic hemangioma, the follow up examination conducted 16 months later revealed that the tumor had grown to 18mm. Doubling time of the tumor was calculated to be 177 days. Because magnetic resonance imaging results were not typical for hepatic hemangioma, hepatocellular carcinoma was suspected and partial hepatectomy was performed. Histologically, the tumor was comprised dense proliferation of small irregular tubules with fibrous stroma. Immunohistochemistry revealed that the carcinoma cells were positive for cytokeratin (CK) 7, CK19, and neurnal cell adhesion molecule. Cells were negative for hepatocyte paraffin 1. Periodic acid-Schiff and Alcian blue staining showed an absence of mucin in the tumor cells, and epithelial membrane antigen was strongly positive on the luminal surface of tubules. These findings were typical of CoCC;therefore, CoCC should be ruled out when dynamic CT images suggest hepatic hemangioma.

Transforming growth factor ß1-induced collagen production in myofibroblasts is mediated by reactive oxygen species derived from NADPH oxidase 4.

Intestinal fibrosis with stricture formation is a severe complication of Crohn's disease (CD). Though new therapeutic targets to enable the prevention or treatment of intestinal fibrosis are needed, markers of this condition and the basic mechanisms responsible have not been established. NADPH oxidase (NOX) 4 has already been reported to play a key role in models of fibrogenesis, including that of the lung. However, its importance in intestinal fibrogenesis remains unclear. In this study, we examined the role of NOX4 in collagen production by intestinal myofibroblasts stimulated with transforming growth factor (TGF)-ß1. Using LmcMF cells, an intestinal subepithelial myofibroblast (ISEMF) line, we first examined the induction of collagen production by TGF-ß1. Subsequently, we investigated the role of NOX4 in TGF-ß1-induced collagen I production in these cells using SB525334 (an SMAD2/3 inhibitor), diphenyleneiodonium (an NOX inhibitor), and Nox4 small interfering RNA (siRNA). Production of collagen was assessed with Sirius red staining, and Nox4 expression was measured by quantitative real-time PCR. Reactive oxygen species (ROS) production was determined using DCFDA and fluorescent microscopy. We observed that TGF-ß1 induced collagen production via NOX4 activation and ROS generation in LmcMF cells. Nox4 siRNA and inhibitors of TGF-ß1 receptor and NOX significantly reduced TGF-ß1-induced ROS and collagen production. Thus, in the present study, we revealed that collagen production in ISEMFs is induced via an NOX4-dependent pathway. This work supports a function for NOX4 in intestinal fibrogenesis and identifies it as a potential therapeutic target in recalcitrant fibrotic disorders of CD patients.

[A case of a gas-forming liver abscess caused by Clostridium perfringens after transcatheter arterial chemoembolization].

An 80-year-old man had a medical history of chronic hepatitis C and pancreatoduodenectomy. We detected recurrence of hepatocellular carcinoma, and performed transcatheter arterial chemoembolization, instead of radiofrequency ablation or surgery, because of the patient's medical history of bile duct reconstruction and liver dysfunction. On the second day, he was diagnosed with a gas-forming liver abscess and underwent liver abscess drainage. Clostridium perfringens and sordellii were detected by aspiration and the blood culture. Meropenem and Clindamycin were administered intravenously. He was treated shortly after the occurrence before the involvement of severe hemolysis and recovered from the acute phase.

Secreted protein acidic and rich in cysteine functions in colitis via IL17A regulation in mucosal CD4+ T cells.

BACKGROUND AND AIM: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycol that regulates cell proliferation, tissue repair, and tumorigenesis. Despite evidence linking SPARC to inflammation, the mechanisms are unclear. Accordingly, the role of SPARC in intestinal inflammation was investigated. METHODS: Colitis was induced in wild-type (WT) and SPARC knockout (KO) mice using trinitrobenzene sulfonic acid (TNBS). Colons were assessed for damage; leukocyte infiltration; Tnf, Ifng, Il17a, and Il10 mRNA expression; and histology. Cytokine profiling of colonic lamina propria mononuclear cells (LPMCs) was performed by flow cytometry. Naïve CD4+ T cells were isolated from WT and SPARC KO mouse spleens, and the effect of SPARC on Th17 cell differentiation was examined. Recombination activating gene 1 knockout (RAG1 KO) mice reconstituted with T cells from either WT or SPARC KO mice were investigated. RESULTS: Trinitrobenzene sulfonic acid exposure significantly reduced bodyweight and increased mucosal inflammation, leukocyte infiltration, and Il17a mRNA expression in WT relative to SPARC KO mice. The percentage of IL17A-producing CD4+ T cells among LPMCs from KO mice was lower than that in WT mice when both groups were exposed to TNBS. Th17 cell differentiation was suppressed in cells from SPARC KO mice. In the T cell transfer colitis model, RAG1 KO mice receiving T cells from WT mice were more severely affected than those reconstituted with cells from SPARC KO mice. CONCLUSIONS: Secreted protein acidic and rich in cysteine accelerates colonic mucosal inflammation via modulation of IL17A-producing CD4+ T cells. SPARC is a potential therapeutic target for conditions involving intestinal inflammation.