Reduced Abundance of Butyrate-Producing Bacteria Species in the Fecal Microbial Community in Crohn's Disease.

BACKGROUND: The global alteration of the gut microbial community (dysbiosis) plays an important role in the pathogenesis of inflammatory bowel diseases (IBDs). However, bacterial species that characterize dysbiosis in IBD remain unclear. In this study, we assessed the alteration of the fecal microbiota profile in patients with Crohn's disease (CD) using 16S rRNA sequencing. SUMMARY: Fecal samples from 10 inactive CD patients and 10 healthy individuals were subjected to 16S rRNA sequencing. The V3-V4 hypervariable regions of 16S rRNA were sequenced by the Illumina MiSeq™II system. The average of 62,201 reads per CD sample was significantly lower than the average of 73,716 reads per control sample. The genera Bacteroides, Eubacterium, Faecalibacterium and Ruminococcus significantly decreased in CD patients as compared to healthy controls. In contrast, the genera Actinomyces and Bifidobacterium significantly increased in CD patients. At the species level, butyrate-producing bacterial species, such as Blautia faecis, Roseburia inulinivorans, Ruminococcus torques, Clostridium lavalense, Bacteroides uniformis and Faecalibacterium prausnitzii were significantly reduced in CD patients as compared to healthy individuals (p < 0.05). These results of 16S rRNA sequencing were confirmed in additional CD patients (n = 68) and in healthy controls (n = 46) using quantitative PCR. The abundance of Roseburia inulinivorans and Ruminococcus torques was significantly lower in C-reactive protein (CRP)-positive CD patients as compared to CRP-negative CD patients (p < 0.05). KEY MESSAGE: The dysbiosis of CD patients is characterized by reduced abundance of multiple butyrate-producing bacteria species.

[THE CURRENT SITUATION OF FOREIGN TUBERCULOSIS PATIENTS AND THEIR CONCURRENT HIV INFECTION IN HOKKAIDO].

BACKGROUND AND PURPOSE: According to recent news, patients with concurrent tuberculosis (TB) and human immunodeficiency virus (HIV) infection are increasingly common worldwide. This study aimed to investigate whether TB/HIV co-infected patients are visiting Hokkaido. METHOD: We conducted a questionnaire survey regarding foreign patients infected with TB or TB/HIV who visited Hokkaido between January 2001 and September 2014. We mailed questionnaires to health centers, AIDS treatment care hospitals, and TB hospitals in Hokkaido prefecture. RESULTS: Seventy-one TB patients were of foreign nationality according to the answers obtained from health centers. Most of them were foreign students or occupational trainees between 20-30 years old. Approximately half these patients were from East Asia, and 7 patients were from Africa. As 21 % of the patients with TB who visited medical examination were over 1 month from disease onset, and the delay in visiting was recognized. The TB infection was mostly detected coincidentally during the physician visit. In the hospital survey, four TB patients with HIV were of foreign nationality. They were also of the age group from 20-30 years and hailed from sub-Saharan Africa. DISCUSSION: During immigration, medical examination by performing a chest radiograph is important. If the immigrant hails from an area where TB and HIV co-infection is common, it is necessary to confirm whether HIV infection is present.

Quantification of Sorafenib in Human Serum by Competitive Enzyme-Linked Immunosorbent Assay.

The multikinase inhibitor sorafenib has been used in the treatment of hepatocellular carcinoma, renal cell carcinoma, and differentiated thyroid carcinoma. Here we have demonstrated the production of the first specific antibody against sorafenib. Anti-sorafenib serum was obtained by immunizing mice with an antigen conjugated with bovine serum albumin and carboxylic modified 4-(4-aminophenoxy)-N-methyl-2-pyridinecarboxamide (AMPC) using the N-succinimidyl ester method. Enzyme labeling of sorafenib with horseradish peroxidase was similarly performed using carboxylic modified AMPC. A simple competitive enzyme-linked immunosorbent assay (ELISA) for sorafenib was developed using the principle of direct competition between sorafenib and the enzyme marker for anti-sorafenib antibody, which had been adsorbed by the plastic surface of a microtiter plate. Serum sorafenib concentrations lower than 0.04 µg/mL were reproducibly measurable using the ELISA. This ELISA was specific to sorafenib and showed very slight cross-reactivity (2.5%) with a major metabolite, sorafenib N-oxide. The values of serum sorafenib levels from 32 patients measured by this ELISA were comparable with those measured by HPLC, and there was a strong correlation between the values determined by the two methods (Y=1.016X-0.137, r=0.979). The specificity and sensitivity of the ELISA for sorafenib should provide a valuable new tool for use in therapeutic drug monitoring and pharmacokinetic studies of sorafenib.

[Cases of Three Patients with Gastric Cancer and Metastasis to the Skeletal Muscle].

Metastasis to the skeletal muscle from gastric cancer is relatively rare. We report cases of 3 patients undergoing chemotherapy for gastric cancer with metastasis to the skeletal muscle. Case 1: A man in his 70s was diagnosed with advanced gastric cancer (cT4N3M1P0, stage IV), with metastasis to the lung, brain, lymph node, and iliopsoas muscle. Case 2: A man in his 60s was diagnosed with advanced gastric cancer (cT3N3M1P0, stage IV), with metastasis to the brain, lung, lymph node, and iliopsoas muscle. Case 3: A man in his 50s was diagnosed with advanced gastric cancer (cT4N3M1P0, stage IV), with metastasis to the urinary duct, lymph node, back muscle, and iliopsoas muscle. All 3 patients died within 7-8 months after the diagnosis due to progressive disease despite chemotherapy. The prognosis of these 3 patients was significantly poorer than that of patients in our hospital with metastasis not involving the skeletal muscle (p<0.01). Accordingly, metastasis to the skeletal muscle may be an adverse prognostic factor in gastric cancer.

[Two cases of successful sorafenib retreatment with the addition of steroid therapy following sorafenib-induced erythema multiforme in two patients with hepatocellular carcinoma].

Erythema multiforme (EM) is a known side effect of sorafenib therapy in cancer patients; at onset, the causative medication should be permanently discontinued. Here we report two cases of hepatocellular carcinoma (HCC) that developed sorafenib-induced EM. In both cases, retreatment with sorafenib combined with steroid therapy achieved effective tumor control without EM recurrence. The first patient was a 72-year-old woman who showed a dramatic response to sorafenib retreatment, with complete remission after 8 months of therapy. There was no rash recurrence after the steroid dose was gradually tapered and stopped. The second patient was a 69-year-old man who responded to sorafenib and exhibited stable disease, with no recurrence of the rash after the steroid dose was tapered. However, mild hand-foot syndrome persisted throughout sorafenib therapy. Although sorafenib should be discontinued if EM occurs, if there is no suitable alternative treatment, retreatment may be considered with steroid cover in patients with unresectable HCC.

Threaded biliary inside stents are a safe and effective therapeutic option in cases of malignant hilar obstruction.

BACKGROUND: Although endoscopic biliary stents have been accepted as part of palliative therapy for cases of malignant hilar obstruction, the optimal endoscopic management regime remains controversial. In this study, we evaluated the safety and efficacy of placing a threaded stent above the sphincter of Oddi (threaded inside plastic stents, threaded PS) and compared the results with those of other stent types. METHODS: Patients with malignant hilar obstruction, including those requiring biliary drainage for stent occlusion, were selected. Patients received either one of the following endoscopic indwelling stents: threaded PS, conventional plastic stents (conventional PS), or metallic stents (MS). Duration of stent patency and the incident of complication were compared in these patients. RESULTS: Forty-two patients underwent placement of endoscopic indwelling stents (threaded PS = 12, conventional PS = 17, MS = 13). The median duration of threaded PS patency was significantly longer than that of conventional PS patency (142 vs. 32 days; P = 0.04, logrank test). The median duration of threaded PS and MS patency was not significantly different (142 vs. 150 days, P = 0.83). Stent migration did not occur in any group. Among patients who underwent threaded PS placement as a salvage therapy after MS obstruction due to tumor ingrowth, the median duration of MS patency was significantly shorter than that of threaded PS patency (123 vs. 240 days). CONCLUSIONS: Threaded PS are safe and effective in cases of malignant hilar obstruction; moreover, it is a suitable therapeutic option not only for initial drainage but also for salvage therapy.

Small-cell Lung Carcinoma with Gastrointestinal Pseudo-obstruction as a Paraneoplastic Neurological Syndrome Elicited by an Immune Checkpoint Inhibitor.

Gastrointestinal pseudo-obstruction (GIPO) is a phenotype of the paraneoplastic neurological syndrome (PNS). We herein report a case of small-cell lung carcinoma (SCLC) with GIPO elicited by an immune checkpoint inhibitor (ICI). A 75-year-old man with SCLC developed intractable intestinal obstruction after receiving one course of anticancer drugs (durvalumab, etoposide, and carboplatin). The serum anti-Hu antibody (Hu-Ab) was positive, and the patient was diagnosed with GIPO. Corticosteroid treatment did not improve the GIPO, and the patient died. There are few reports of GIPO after ICI treatment in patients with lung cancer, so a further investigation will be required to elucidate the mechanism by which ICIs elicit PNS. Checking for neuronal antibodies may help identify patients with SCLC who are at risk of developing PNS due to ICI treatment.

The severity of dextran sodium sulfate-induced colitis can differ between dextran sodium sulfate preparations of the same molecular weight range.

BACKGROUND: We hypothesized that the severity of dextran sodium sulfate (DSS)-induced colitis could differ between DSS preparations of the same molecular weight, and that this difference may be affected by the sulfur content. To test this, we used three DSS preparations of similar molecular weights but with different sulfur contents. METHODS: Three DSS preparations with molecular weights of 40,000 to 50,000 were tested: MP Biomedicals (MP Bio), USB (USB), and The Lab Depot (The Lab). Epithelial cell lines were used to assess the levels of poly (ADP-ribose) polymerase (PARP) in the presence of 2.0% DSS in vitro. Eight-week-old female C57/B6 mice were fed 2.0% DSS in water for 1 week, and then sacrificed to investigate the effects of the DSS preparations in vivo. RESULTS: In vitro experiments using CaCo-2 and CMT-93 cells revealed decreased PARP levels from all DSS preparations. Notably, the PARP level was significantly decreased in CaCo-2 cells treated with DSS from USB as compared to The Lab Mice treated with The Lab DSS had significantly decreased body weight losses on day 7 as compared to mice receiving DSS from MP Bio and USB. This result was supported by their DAI score, colon weight/length ratio, and histological scores. CONCLUSION: The severity of colitis can differ between similar DSS preparations of the same molecular weight range. This difference in colitogenic properties may be affected by the total sulfur content of each DSS preparation.

Expression of IL-24, an activator of the JAK1/STAT3/SOCS3 cascade, is enhanced in inflammatory bowel disease.

IL-24 is a member of the IL-10 family of cytokines. In this study, we investigated IL-24 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD), and characterized the molecular mechanisms responsible for IL-24 expression in human colonic subepithelial myofibroblasts (SEMFs). IL-24 expression in the IBD mucosa was evaluated by immunohistochemical methods. IL-24 mRNA and protein expression was determined by real-time PCR and ELISA, respectively. AP-1 and C/EBP DNA-binding activity and IL-24 promoter activity were assessed by EMSA analysis and a reporter gene assay, respectively. IL-24 mRNA expression was significantly elevated in active lesions from patients who have ulcerative colitis and Crohn's disease. Colonic SEMFs were identified as a major source of IL-24 in the mucosa. IL-1beta, but not IL-17A, TNF-alpha, or IFN-gamma, significantly enhanced IL-24 mRNA and protein expression in isolated colonic SEMFs. The IL-1beta-induced IL-24 mRNA expression was mediated by the activation of the transcription factors, AP-1 and C/EBP-beta. Induction of IL-24 mRNA stabilization was also involved in the effects of IL-1beta. IL-24 induced JAK1/STAT-3 phosphorylation and SOCS3 expression in HT-29 colonic epithelial cells. IL-24 did not modulate the proliferation of HT-29 cells, but significantly increased the mRNA expression of membrane-bound mucins (MUC1, MUC3, and MUC4). IL-24 derived from colonic SEMFs acts on colonic epithelial cells to elicit JAK1/STAT-3 activation and the expression of SOCS3 and mucins, supporting their suppressive effects on mucosal inflammation in IBD.

Repeated treatment with gefitinib and alectinib in a patient with multiple EGFR-mutant and ALK-mutant lung adenocarcinomas: A case report.

Multiple EGFR-mutant and ALK-mutant lung cancers are rare, and standard treatment has not been established because of the small number of cases. A 79-year-old man was found to harbor nodular shadows in right S1, right S5, and left S3. He was surgically diagnosed with stage IIB (pT3N0M0) EGFR G719X-mutant lung adenocarcinoma in left S3 and stage IA1 (pT1aN0M0) ALK-mutant lung adenocarcinoma in right S5. Owing to the relapse of the EGFR-mutant adenocarcinoma, gefitinib treatment was commenced 3 months postoperatively. The tumor shrank temporarily; however, the nodular shadow in the right S1 and #3a lymph nodes were found to increase in size. He was diagnosed with adenosquamous carcinoma in right S1 and relapsing ALK-mutant adenocarcinoma in #3a lymph node. Gefitinib treatment was continued, but due to a renewed increase in the size of the #3a lymph node, the drug was changed to alectinib 16 months postoperatively. Subsequently, the EGFR-mutant adenocarcinomas were found to increase in left S1 despite the decrease in the #3a lymph node size. Nineteen months after the first surgery, the treatment was changed to gefitinib, and repeated treatment with this drug and alectinib administered every 2 months was continued. This approach enabled 39 months of progression-free survival, and no serious adverse events were observed.

[Surgical treatment for recurrent pulmonary carcinoma including same and different cell types].

There are many problems regarding diagnosis of the next lung cancer as local recurrence, metastasis or 2nd primary and there is a limit to only morphologic findings. It may be necessary to examine oncogene abnormalities for example p53 mutation. From the above-mentioned facts, this study distinguished the recurrent resected lung tumors between same (As: n = 19) and different (Ah: n = 8) cell types from the 1st lung cancer. These 2 groups were compared each other and with group B, which was treated to recurrent lung cancer only with chemotherapy and/or radiation, and group C, which was not treated. On 5-year survival after the 1st operation, group As was 78.9%, group Ah was 75.0%, group B was 15.0%, group C was 0%. On 5-year survival after the 2nd operation, group As was 21.1%, group Ah was 42.9%. There were long intervals between the 1st and the 2nd operations (overall mean 56.1+/- 45.6 month, max 190 month), therefore we must follow up on patients undergone resection of lung cancer at the long-term periods. Recent amelioration of chemotherapy and radiotherapy can keep patients with recurrent lung cancer survive by over 5 years. It is important not only to perform an aggressive 2nd operation for recurrent lung cancer but also to estimate post-2nd-operative lung function for selection of operative procedure and to prefer multidisciplinary treatment.

Long-term response with durvalumab after chemoradiotherapy for pulmonary pleomorphic carcinoma: A case report.

Pulmonary pleomorphic carcinoma (PPC) is a non-small-cell lung cancer, resistant to chemotherapy and no standard therapy has as yet been established. We herein report the case of a 59-year-old man with PPC who showed a long-term response with durvalumab after chemoradiotherapy. He was referred to our hospital with a mass shadow at the right upper lung. PPC clinical stage IIIB was diagnosed, and the tumor proportion score of programmed death-ligand 1 (PD-L1) was 100%. Six days after transbronchial biopsy, he had difficulty walking owing to sensory abnormalities. We found that the primary tumor had invaded the spinal cord and compressed the cord at T1-T4, resulting in the abnormalities. He underwent tumor resection and received chemotherapy involving cisplatin (CDDP) + S-1 and concurrent radiotherapy (66 Gy). Subsequently, durvalumab treatment as consolidation therapy was commenced. After one year of durvalumab treatment had been completed, he had no apparent signs of relapse or severe adverse events. This case suggests that a long-term response can be achieved with durvalumab after chemoradiotherapy for stage III inoperable PPC showing high PD-L1 expression. KEY POINTS: Significant findings of the report A long-term response might be achieved with durvalumab after chemoradiotherapy in patients with stage III inoperable pulmonary pleomorphic carcinoma showing high expression of programmed death-ligand What this study adds It is possible to continue durvalumab treatment for one year without any severe adverse events. Although pulmonary pleomorphic carcinoma is considered to have a poor prognosis, the combination therapy of immune checkpoint inhibitors and radiotherapy may be an effective treatment option.

Inhibitory effects of short-chain fatty acids on matrix metalloproteinase secretion from human colonic subepithelial myofibroblasts.

BACKGROUND AND AIMS: Short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate, are the major by-product of bacterial fermentation of dietary fiber in the colon. In this report, we investigated how SCFAs modulate matrix metalloproteinase (MMP) secretion from human colonic subepithelial myofibroblasts (SEMFs). MATERIALS AND METHODS: SEMFs were identified by expression of alpha-smooth muscle actin and vimentin. Cytokine-induced MMP-1 and MMP-3 levels were determined by enzyme-linked immunosorbent assay. Cytokine-induced MMP mRNA expression was analyzed by RT-PCR and real-time PCR methods. RESULTS: Acetate had no effect on MMP secretion. Propionate and butyrate significantly attenuated IL-1 beta- and TNF-alpha-induced MMP-1 and MMP-3 secretion. Similar responses were also observed at the mRNA levels. Propionate and butyrate did not modulate IL-1 beta- and TNF-alpha-induced activation of mitogen-activated protein kinases (MAPKs), which play a crucial role in MMP induction. Trichostatin A, a histone-deacetylase inhibitor, reduced IL-1 beta-induced MMP-1 and MMP-3 mRNA expression, and suppressed TNF-alpha-induced MMP-3 mRNA expression. CONCLUSION: SCFAs play an anti-inflammatory role through suppression of MMP secretion in the colon. Inhibitory effects of SCFAs on MMP secretion might be associated with their action of histone hyperacetylation.

Amphiregulin and epiregulin expression in neoplastic and inflammatory lesions in the colon.

Amphiregulin and epiregulin belong to the epidermal growth factor family and mediate the biological functions of epithelial and mesenchymal cells through epidermal growth factor receptors. In this study, we evaluated the amphiregulin and epiregulin expression in neoplastic and inflammatory lesions from the human colon. Surgically-obtained specimens were stained using standard immunohistochemical procedures. Amphiregulin and epiregulin were not expressed in the normal colonic mucosa, but were clearly detectable in adenomas and carcinomas. Weak immunostaining was also detected in mesenchymal cells from the tumor tissues. In the active mucosa of patients with ulcerative colitis and Crohn's disease, amphiregulin was mainly expressed by the epithelial cells. In addition, positive immunostaining was also detectable in the surrounding mesenchymal cells. In conclusion, amphiregulin and epiregulin may play important roles in colonic tumor growth and mucosal repair in the inflamed mucosa of inflammatory bowel disease.

Germinated barley foodstuff ameliorates inflammation in mice with colitis through modulation of mucosal immune system.

OBJECTIVE: Germinated barley foodstuff (GBF) is a prebiotic product made from malt which contains glutamine-rich protein and hemicellulose-rich fiber. Although GBF has been observed to attenuate colonic mucosal inflammation and bowel movements in ulcerative colitis, both experimentally and clinically, the details of the immune response remain elusive. The aim of this study was to investigate the effects of GBF on the colonic epithelium immune response in a CD45RB(high) T cell chronic colitis model. MATERIAL AND METHODS: Colitis was induced by transferring CD4+ CD45RB(high) T cells to severe combined immunodeficiency (SCID) mice (control n=8, GBF n=8) and the effects of GBF on the colitis were evaluated. The evaluation included measurement of body-weight, occult blood tests, histological examination, mucosal cytokine reverse transcription-polymerase chain reaction (RT-PCR) analysis (interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta)) as well as IL-6 measurements. RESULTS: Seven weeks after transferring the above cells, body-weight loss and occult blood were significantly reduced in the mice that had been fed with GBF. In these mice, there were also significant reductions in IFN-gamma mRNA expressions and IL-6 in the colonic mucosa, as compared with the control group. GBF also significantly attenuated, mucosal damage and mucin positive goblet cell depletion. Conversely, TGF-beta expression significantly increased in the GBF group, compared with the control group. CONCLUSIONS: In this preliminary study using an experimental model in which colitis was induced by transferring CD4+ CD45RB(high) T cells to SCID mice, GBF reduced inflammation by modulating the colonic microflora.

Mucosal cytokine network in inflammatory bowel disease.

Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) are characterized by ongoing mucosal inflammation in which dysfunction of the host immunologic response against dietary factors and commensal bacteria is involved. The chronic inflammatory process leads to disruption of the epithelial barrier, and the formation of epithelial ulceration. This permits easy access for the luminal microbiota and dietary antigens to cells resident in the lamina propria, and stimulates further pathological immune cell responses. Cytokines are essential mediators of the interactions between activated immune cells and non-immune cells, including epithelial and mesenchymal cells. The clinical efficacy of targeting TNF-alpha clearly indicates that cytokines are the therapeutic targets in IBD patients. In this manuscript, we focus on the biological activities of recently-reported cytokines [Interleukin (IL)-17 cytokine family, IL-31 and IL-32], which might play a role through interaction with TNF-alpha in the pathophysiology of IBD.

FR167653, a p38 mitogen-activated protein kinase inhibitor, aggravates experimental colitis in mice.

AIM: To investigate the effects of FR167653 on the development of dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: BALB/c mice were fed rodent chow containing 3.5% (wt/wt) DSS. The recipient mice underwent intra-peritoneal injection of vehicles or FR167653 (30 mg/kg per day). The mice were sacrificed on day 14, and the degree of colitis was assessed. Immunohistochemical analyses for CD4(+) T cell and F4/80(+) macrophage infiltration were also performed. Mucosal cytokine expression was analyzed by RT-PCR. RESULTS: The body weight loss was more apparent in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. The colon length was shorter in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. Disease activity index and histological colitis score were significantly higher in FR167653- than in vehicle-treated DSS animals. Microscopically, mucosal edema, cellular infiltration (CD4 T cells and F4/80 macrophages), and the disruption of the epithelium were much more severe in FR167653-treated mice than in controls. Mucosal mRNA expression for interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were found to be markedly reduced in FR167653-treated DSS mice. CONCLUSION: Treatment with FR167653 aggravated DSS colitis in mice. This effect was accompanied by a reduction of mucosal IL-1beta and TNF-alpha expression, suggesting a role of p38 mitogen-activated protein kinase (MAPK)-mediated proinflammatory cytokine induction in host defense mechanisms.

Poorer Prognosis of Idiopathic Pleuroparenchymal Fibroelastosis Compared with Idiopathic Pulmonary Fibrosis in Advanced Stage.

Objective: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare disease characterized by predominant upper lobe pulmonary fibrosis of unknown etiology. However, the prognosis of IPPFE has not been discussed. We investigated the clinical characteristics and prognostic factors of IPPFE and idiopathic pulmonary fibrosis (IPF). Methods: We performed a retrospective cohort study on 375 consecutive idiopathic interstitial pneumonia patients between April 2004 and December 2014. Among them, we diagnosed IPPFE and IPF patients using high-resolution computed tomography radiological criteria. Results: Twenty-nine IPPFE patients (9 males, 20 females) and 67 IPF patients (54 males, 13 females) were enrolled. IPPFE patients were significantly more likely to be females and nonsmokers and had lower body mass index, lower values of predicted percentage of forced vital capacity (%FVC), and a higher residual volume-to-total lung capacity ratio than IPF patients. Survival analysis revealed that they had significantly poorer prognosis than IPF patients in GAP (gender, age, and physiology) stages II + III. %FVC and GAP index independently predict mortality in patients with IPPFE. Conclusions: Patients with IPPFE showed poorer prognosis in the advanced stage than patients with IPF. %FVC and GAP index are independent predictors of survival in patients with IPPFE.

Interleukin-31 stimulates production of inflammatory mediators from human colonic subepithelial myofibroblasts.

Interleukin (IL)-31 is mainly produced by CD4+ T cells, in particular T cells skewed toward a Th2 phenotype. Here we report for the first time that IL-31 stimulates secretion of proinflammatory cytokines, chemokines and matrix metalloproteinases (MMPs) from human colonic subepithelial myofibroblasts (SEMFs). The effects of IL-31 were investigated by cDNA microarrays, enzyme-linked immunosorbent assay, and real-time PCR. IL-31 effectively induced chemokines [IL-8, GRO-alpha (growth-related oncogene-alpha), MCP-3 (monocyte chemoattractant protein-3), CXCL3, CCL13 and CCL15], proinflammatory cytokines (IL-6, IL-16 and IL-32) and matrix metalloproteinases (MMP-1, MMP-3, MMP-25 and MMP-7). IL-31 dose-dependently induced secretion of IL-6, IL-8, GRO-alpha, MCP-3, MMP-1 and MMP-3. The effects of IL-31 were comparable to the effects of IL-17A. IL-31 and IL-17A showed additive effects on IL-6, IL-8, GRO-alpha, MCP-3, MMP-1 and MMP-3 secretion. In conclusion, we demonstrated that IL-31 is a potent inducer of proinflammatory mediators in human colonic SEMFs. IL-31 may function as a proinflammatory cytokine derived from Th2 cells.