Difference in DRB1~* gene polymorphisms between Han and Uyghur ulcerative colitis patients in China

AIM:To evaluate the association between HLA-DRB1 alleles and Han and Uyghur ulcerative colitis (UC) patients residing in the Xinjiang Uyghur Autonomous Region of China. METHODS:In this study, 102 UC patients (53 Han including 22 men and 31 women, and 49 Uyghur patients including 25 men and 24 women; aged 48.07 ± 15.83 years) and 310 age- and sex-matched healthy controls were enrolled in the Department of Gastroenterology, Xinjiang People’s Hospital of China from January 2010 to May 2011. UC was diagnosed based on the clinical, endoscopic and histological findings following Lennard-Jones criteria. Blood samples were collected and genomic DNA was extracted by routine laboratory methods, and both polymerase chain reaction and gene sequencing were used to identify HLA-DRB1 allele variants. The potential association between genetic varia-tion and UC in Han and Uyghur patients was examined. There were no statistical differences in HLA-DRB1 allele frequencies in Han UC patients. RESULTS:There was no significant difference in the sex ratio between the controls and UC patients (P = 0.740). In Han patients with UC (n = 53), HLA-DRB1 *03 , *13 allele frequencies were lower than in healthy controls (n = 161), but not statistically significant, and HLA-DRB1*04*11*14 allele frequencies were higher than in healthy controls, but without statistical significance. Differences between Uyghur UC patients and the control group were observed for HLA-DRB1*04 and HLA-DRB1*13 , both showed a greater frequency in UC patients (10.21% vs 2.69%, P = 0.043; 14.29% vs 4.03%, P = 0.019). HLA-DRB1*14 also showed a greater frequency in UC patients (14.29% vs 2.69%, P = 0.006). The frequencies of DRB1*04 , *13*14 alleles were increased in Uyghur UC patients compared with normal controls. The frequency of DRB1 * 08 was decreased in Uyghur UC patients compared with normal controls. HLA-DRB1 alleles showed no association with UC in Han patients. There were no statistical differences in HLA-DRB1 allele frequencies in Han UC patients. The frequenci     

Epithelial markers of colorectal carcinogenesis in ulcerative colitis and primary sclerosing cholangitis

AIM:To evaluate the expression of epithelial markers of colorectal carcinogenesis in patients with long-term ulcerative colitis(UC) and primary sclerosing cholangitis(PSC) before and after transplantation.METHODS:Eight patients with UC and PSC prior to liver transplantation(PSC-UC),22 patients with UC after liver transplantation for PSC(OLT),9 patients with active ulcerative colitis without PSC(UCA),7 patients withUC in remission(UCR) and 10 controls(N) underwent colonoscopy with multiple biopsies.Specimens were analysed histologically and semi-quantitatively immunohistochemically for p53,Bcl-2 and cyclooxygenase-2(COX-2) markers.Statistical analysis was performed by Kruskal-Wallis and Fisher’s exact tests.RESULTS:PSC-UC had a statistically significantly higher expression of p53 in the nondysplastic mucosa as compared to OLT,UCA,UCR and N(P < 0.05).We also found a statistically significant positive correlation between the incidence of PSC and the expression of p53(P < 0.001).UCA had a higher p53 expression as compared to UCR.OLT had a significantly lower expression of p53 as compared with PSC-UC(P < 0.001).Bcl-2 had a significant higher bcl-2 expression as compared with controls.No difference in COX-2 expression between PSC-UC,UCR and UCA was found.UCA had higher COX-2 expression as compared to UCR.We also found a statistically significant positive correlation between the expression of COX-2 and p53.Patients after liver transplantation for PSC had a statistically significantly lower expression of the p53 compared with PSCUC(P < 0.001).PSC-UC had the same inflammatory endoscopic activity as OLT and UCR when evaluated with the Mayo score.CONCLUSION:Our study shows that the nondysplatic mucosa of UC patients with PSC is characterised by a higher expression of the tumour suppressor gene p53,suggesting a higher susceptibility of cancer.This p53 overexpression correlates with the presence of PSC whilst it is not present in patients with UC after liver transplantation for PSC.     

IL-23／IL-17炎症轴在溃疡性结肠炎中的作用

目的探讨IL-23／IL-17炎症轴在溃疡性结肠炎（UC）中的变化及意义。方法按照2007年济南标准选择UC组患者20例,对照组16例。利用细胞内细胞因子染色和四色荧光抗体流式细胞术对肠黏膜固有层单个核细胞作表型分析,比较Th1、Th2、Th17比例的改变。Westernblot检测肠黏膜IL-17、IL-23表达。数据以中位数和四分位间距即M（QR）形式表示,行相关统计。结果（1）肠黏膜中Th17的比例在UC组中较对照组明显增加（P〈0．05）,为3．75％比1．25％,且重度活动较轻度活动患者增加明显（P〈0．05）,为8．30％比1．20％。肠黏膜中Th1的比例在UC组和对照组中分别为13．60％和9．10％,Th2的比例在UC和对照组中分别为1．10％和1．15％,差异均无统计学意义（P〉0．05）,不同活动度患者间差异亦无统计学意义（P〉0．05）。（2）UC组患者肠黏膜中IL-17表达较对照组明显升高（P〈0．05）,为0．20％比0．10％,且IL-17表达与UC患者疾病评分呈正相关（r=0．50,P=0．02）。（3）IL-23表达在UC组和对照组分别是0．13％和0．07％,差异有统计学意义（P〈0．05）。结论IL-23／IL-17炎症轴在溃疡性结肠炎的发病中具有重要作用,它可能成为UC治疗的有效靶点。     

白细胞介素-23在炎症性肠病的表达升高并诱导促炎细胞因子分泌

目的 通过分析白细胞介素(IL)-23p19及其受体(IL-23R)在炎症性肠病(IBD)患者中的表达,研究IL-23对IBD患者外周血T细胞激活和效应应答的影响,探讨其在疾病发生过程中的免疫病理作用.方法 收集12例克罗恩病(CD)患者、25例溃疡性结肠炎(UC)患者和20名健康者外周血和肠黏膜组织活检标本,使用免疫组化染色和逆转录(RT)-PCR分析IL-23p19表达,分离外周血单个核细胞(PBMC)和肠黏膜固有层内单个核细胞(LPMC),利用流式细胞仪检测IL-23R在CD4+、CD8+T细胞和自然杀伤(NK)细胞表面表达.体外培养PBMC,使用IL-23和抗CD3单抗体外刺激,使用酶联免疫吸附试验检测肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ和白细胞介素(IL)-2分泌.结果 IBD患者炎症肠黏膜组织内IL-23p19蛋白和mRNA表达水平比健康对照者显著升高(P<0.05).IL-23R在IBD患者外周血和肠黏膜固有层组织内CD4+、CD8+T细胞和NK细胞表达水平也比健康者显著升高(P<0.05).体外培养PBMC,使用IL-23刺激,发现IL-23可显著诱导IBD患者,尤其是CD患者PBMC激活,分泌高水平TNF-α、IFN-γ和IL-2(P<0.05).结论 IL-23及其受体在IBD患者炎症肠黏膜组织中表达升高,IL-23可诱导IBD患者淋巴细胞分泌高水平的炎性介质,提示IL-23参与了肠黏膜炎症损伤,阻断IL-23生物学效应可能治疗IBD.     

Effects of baicalin in CD4 + CD29 + T cell subsets of ulcerative colitis patients

AIM: To evaluate the role of baicalin in ulcerative colitis (UC) with regard to the CD4⁺CD29⁺ T helper cell, its surface markers and serum inflammatory cytokines.METHODS: Flow cytometry was used to detect the percentage of CD4⁺CD29⁺ cells in patients with UC. Real time polymerase chain reaction was used to detect expression of GATA-3, forkhead box P3, T-box expressed in T cells (T-bet), and retinoic acid-related orphan nuclear hormone receptor C (RORC). Western blotting was used to analyze expression of nuclear factor-κB (NF-κB) p65, phosphorylation of NF-κB (p-NF-κB) p65, STAT4, p-STAT4, STAT6 and p-STAT6. The concentrations of interferon-γ (IFN-γ), interleukin (IL)-4, IL-5, IL-6, IL-10 and TGF-β in serum were determined by ELISA assay.RESULTS: The percentages of CD4⁺CD29⁺ T cells were lower in treatment with 40 and 20 μmol/L baicalin than in the treatment of no baicalin. Treatment with 40 or 20 μmol/L baicalin significantly upregulated expression of IL-4, TGF-β1 and IL-10, increased p-STAT6/STAT6 ratio, but downregulated expression of IFN-γ, IL-5, IL-6, RORC, Foxp3 and T-bet, and decreased ratios of T-bet/GATA-3, p-STAT4/STAT4 and p-NF-κB/NF-κB compared to the treatment of no baicalin.CONCLUSION: The results indicate that baicalin regulates immune balance and relieves the ulcerative colitis-induced inflammation reaction by promoting proliferation of CD4⁺CD29⁺ cells and modulating immunosuppressive pathways.     

Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results,mucosal healing,and risk of relapse

AIM: To assess the risk of relapse in ulcerative colitis(UC) patients in clinical remission using mucosal status and fecal immunochemical test(FIT) results. METHODS: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores(MESs) and FIT results.RESULTS: Patients with an MES of 0(n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3(n = 100, 52%)(HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result(fecal hemoglobin concentrations ≤ 100 ng/m L) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score(HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse(HR = 0.11, 95%CI: 0.04-0.23).CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing(MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.     

Plasma interleukin-18 reflects severity of ulcerative colitis

AIM: The aim of this study was to evaluate the association between ulcerative colitis activity and plasma or mucosal concentrations of interleukin (IL)-18. METHODS: 11-18 concentrations were measured in plasma and mucosal samples from 15 patients with active ulcerative colitis (UC). RESULTS: The mean plasma concentration of IL-18 measured in all patients (422±88 pg/mL) doubled the mean value in healthy controls (206±32 pg/mL); however, the difference was not statistically significant. Plasma IL-18 levels revealed a significant positive correlation with scored endoscopic degree of mucosal injury, disease activity index, clinical activity index and C-reactive protein concentration. The mean concentration of plasma IL-18 was significantly higher in patients with severe ulcerative colitis (535±115 pg/mL) than in patients with mild ulcerative colitis (195±41 pg/mL), and in healthy controls. Although the mucosal mean IL-18 concentration in severe ulcerative colitis (2 523±618 pg/mg protein) doubled values observed in mild one (1347±308 pg/mg protein), there was no statistically significant difference. CONCLUSION: Plasma IL-18 can be considered as a surrogate marker helpful in evaluation of ulcerative colitis activity.     

Effects of adacolumn selective leukocytapheresis on plasma cytokines during active disease in patients with active ulcerative colitis

AIM: To investigate the relationship between ulcerative colitis (UC) clinical activity index (CAI) and circulating levels of IL-1ra, IL-10, IL-6 and IL-18. METHODS: Blood levels of IL-lra, IL-10, IL-6 and IL-18 were measured in 31 patients with active UC, the mean CAI was 11.1, ranging from 5-25; and 12 healthy individuals as controls. Patients were given granulocyte and monocyte adsorptive apheresis (GMA) with Adacol-umn. Leucocytes which bear the FcyR and complement receptors were adsorbed to the column leucocytapher-esis carriers. Each patient could receive up to 11 GMA sessions over 8 wk. RESULTS: We found strong correlations between CAI and IL-10 (r = 0.827, P < 0.001), IL-6 (r = 0.785, P < 0.001) and IL-18 (r = 0.791, P < 0.001). IL-lra was not correlated with CAI. Following GMA therapy, 24 of the 31 patients achieved remission and the levels of all 4 cytokines fell to the levels in healthy controls. Further, blood levels of IL-lra and IL-10 increased at the column outflow and inflow at 60 min suggesting release from leucocytes that adhered to the carriers. CONCLUSION: Elevated blood levels of IL-6 and IL-18 together with peripheral blood granulocytes and mono-cytes/macrophages in patients with active UC show acti-vative behaviour and increased survival time can be pro-inflammatory and the targets of GMA therapy.     

PTPN22在溃疡性结肠炎中的表达及其临床意义

背景:溃疡性结肠炎(UC)的发生、发展与T细胞过度活化有关,蛋白酪氨酸磷酸酶非受体型22(PTPN22)参与T细胞活化的负性调节。目的:探讨PTPN22在UC中的表达及其临床意义。方法:纳入2010年7月～2012年7月武汉市中心医院、武汉大学中南医院就诊的UC患者60例,同时纳入35例IBS患者作为对照组。采用实时定量PCR法检测患者肠黏膜PTPN22 mRNA表达水平。采用全自动红细胞沉降系统分析仪检测血清ESR水平。采用速率散射比浊法检测血清CRP水平。结果:活动期UC患者肠黏膜PTPN22 mRNA表达水平与缓解期UC患者和对照组相比显著升高(P=0.007;P=0.021)。UC患者肠黏膜PTPN22 mRNA表达水平与血清ESR和CRP水平呈正相关(r=0.63,P=0.005;r=0.58,P<0.01)。UC患者疾病严重程度和病变范围与肠黏膜PTPN22 mRNA表达水平呈正相关(r=0.51,P<0.01;r=0.44,P<0.01)。中重度UC患者肠黏膜PTPN22 mRNA表达水平与轻度UC患者相比显著升高(P=0.005),病变位于广泛结肠者肠黏膜PTPN22 mRNA表达水平与病变位于左半结肠和直肠者相比显著升高(P=0.029;P=0.008)。结论:PTPN22 mRNA表达水平与UC疾病活动性、严重程度和病变范围相关。PTPN22可能在UC发病机制中发挥重要作用。     

白细胞介素-18基因单核苷酸多态性及其血清含量与溃疡性结肠炎的相关性

目的 探讨白细胞介素(IL)-18基因单核苷酸多态性(SNP)及其血清含量与溃疡性结肠炎(UC)的相关性.方法 采用PCR扩增和直接测序法检测50例UC患者及128名健康对照者的IL-18基因5'端4个SNP位点(rs187238 G/C、rs5744228 G/A、rs360718 A/C、rs360717 G/A),同时检测受试者血清IL-18含量.结果 UC组血清IL-18含量明显高于对照组,两组间差异有统计学意义(3029.9±111.7)pg/ml比(133.2±39.4)pg/ml,(P<0.01).rs187238 C、rs360718 C、rs360717 A位点与UC显著相关(X~2=9.26,P<0.01),该3个位点的单倍体型频率在UC组和对照组间差异亦有统计学意义(X~2=7.04,P<0.01).与对照组相比,UC组含等位基因型C者的血清IL-18含量明显升高(P<0.05).结论 IL-18基因的SNP与其血清含量存在相关性,提示其基因位点多态性及血清含量可能与UC易感性相关.     

白细胞介素-25在炎症性肠病患者中的表达及临床意义

目的 通过检测白细胞介素(IL)-25在炎症性肠病(IBD)患者肠黏膜及血清中的表达水平,探讨其在IBD发病过程中的作用及意义.方法 收集12例溃疡性结肠炎(UC)患者、16例克罗恩病(CD)患者及13例对照者的内镜肠黏膜活检标本,采用荧光定量PCR技术检测肠黏膜内IL-25 mRNA的表达情况,免疫组化技术分析IL-25在肠黏膜中的原位表达;同期收集20例UC、24例CD患者及20名健康对照者血清标本,采用酶联免疫吸附测定(ELISA)检测血清中IL-25水平.结果 与健康对照组相比,UC及CD患者肠黏膜组织内IL-25 mRNA表达显著降低(P＜0.05),UC及CD组间的表达量差异无统计学意义(P＞0.05).免疫组化分析显示IL-25阳性细胞在正常肠黏膜固有层内有较多表达,同时黏膜内的肠上皮细胞也存在IL-25低表达,UC及CD患者肠黏膜IL-25蛋白表达量显著降低(P＜0.05),UC及CD组间的表达量差异无统计学意义(P＞0.05).ELISA显示UC及CD患者血清中IL-25表达量显著低于健康对照组(P＜0.05).结论 IL-25在IBD患者肠黏膜及血清中表达显著降低,提示IL-25表达缺陷与IBD的发生发展密切相关,IL-25有可能成为IBD治疗的新靶点.     

Neurotensin receptor 1 overexpression in inflammatory bowel diseases and colitis-associated neoplasia

AIM: To explore the association of neurotensin receptor 1 (NTSR1) with inflammatory bowel diseases (IBD) and colitis-associated neoplasia. METHODS: NTSR1 was detected by immunohistochemistry in clinical samples of colonic mucosa with IBD colitis, colitis-associated raised low-grade dysplasia (LGD) including dysplasia-associated lesions or masses (DALMs, n = 18) and adenoma-like dysplastic polyps (ALDPs, n = 4), colitis-associated high-grade dysplasia (HGD, n = 11) and colitis-associated colorectal carcinoma (CACRC, n = 13), sporadic colorectal adenomatous polyp (SAP, n = 17), and sporadic colorectal carcinoma (SCRC, n = 12). The immunoreactivity of NTSR1 was semiquantitated (as negative, 1+, 2+, and 3+) and compared among different conditions.RESULTS: NTSR1 was not detected in normal mucosa but was expressed similarly in both active and inactive colitis. LGD showed a significantly stronger expression as compared with non-dysplastic colitic mucosa, with significantly more cases showing > 2+ intensity (68.75% in LGD vs 32.26% in nondysplastic mucosa, P = 0.001). However, no significant difference existed between DALMs and ALDPs. CACRC and HGD showed a further stronger expression, with significantly more cases showing 3+ intensity than that in LGD (61.54% vs 12.50% for CACRC vs LGD, P = 0.022; 58.33% vs 12.50% for CACRC/HGD vs LGD, P = 0.015). No significant difference existed between colitis-associated and non-colitic sporadic neoplasia. CONCLUSION: NTSR1 in colonic epithelial cells is overexpressed in IBD, in a stepwise fashion with sequential progress from inflammation to dysplasia and carcinoma.     

溃疡性结肠炎患者炎症黏膜中IL-6、L-23的表达及其临床意义

研究显示促炎细胞因子在溃疡性结肠炎（UC）的发病机制中起重要作用。目的：探讨UC患者炎症黏膜中白细胞介素．6（IL-6）、IL．23的表达情况及其临床意义。方法：选取42例UC患者（轻、中、重度活动期分别为9例、10例和13例．缓解期10例）于内镜下取结直肠炎症黏膜活检标本．另取18名健康志愿者的结肠黏膜作为正常对照。以免疫组化方法检测黏膜细胞因子IL-6、IL-23表达。结果：轻、中、重度活动期UC患者IL-6、IL-23表达量依次增高,组间两两比较差异均有统计学意义（P〈O．05）,且均显著高于缓解期患者和正常对照组（P〈0．05）;缓解期患者仅IL-23表达量显著高于正常对照组（P〈O．05）,IL-6表达量与正常对照组无明显差异。结论：IL-6和IL-23在UC的发生、发展中起重要作用．两者的黏膜表达水平可反映UC疾病活动度。     

Evaluation of the IL-2/IL-2R system in patients with liver cirrhosis or carcinoma

AIM: To evaluate the interleukin-2/interleukin-2 receptor (IL-2/IL-2R) system in patients with liver cirrhosis or carcinoma, and compare the immune function in those patients. The clinical significance of our results is also discussed. METHODS: Fifty patients with liver cirrhosis (LC), 50 patients with hepatocellular carcinoma (HCC), and 30 normal control subjects were studied. Cellular expression of the interleukin-2 receptor (mIL-2R) was examined by immunofluorescence, and the serum levels of IL-2 and soluble interleukin-2 receptor (sIL-2R) were measured by ELISA. RESULTS: The levels of IL-2 and mIL-2R expression in carcinoma patients were significantly lower than those in both patients with cirrhosis (P < 0.01) and control subjects (P < 0.01). The serum levels of IL-2 and the expression of mIL-2R in patients with cirrhosis were also lower than those in normal control subjects (P < 0.05). The serum levels of sIL-2R in carcinoma patients were significantly higher than those in both cirrhosis patients (P < 0.05) and control subjects (P < 0.01), and the sIL-2R levels in cirrhosis patients were higher than those in control subjects (P < 0.05). CONCLUSION: Patients with liver cirrhosis or carcinoma both have decreased immune function; however, this decrease is more pronounced in carcinoma patients. Such similarities in immune disturbances may be an important factor affecting the development of carcinoma in a cirrhotic liver.     

Cytomegalovirus positive ulcerative colitis:A single center experience and literature review

AIM:To compare the clinical outcome of cytomegalovirus(CMV)-positive ulcerative colitis(UC) patients with and without antiviral therapy.METHODS:This was a retrospective case-controlled study.The database of UC patients in our institution was scanned for documented presence of CMV on colonic biopsies.Demographics,clinical data,endoscopy findings and pathology reports were extracted from the patients’ charts and electronic records.When available,the data from colonoscopies preceding and following the diagnosis of colonic CMV infection were also ex-tracted.The primary outcomes of the study were colectomy/death during hospitalization and the secondary outcomes were colectomy/death through the course of the follow-up.RESULTS:Thirteen patients were included in the study,7(53.5%) of them were treated with gancyclovir and 6(46.5%) were not.Patients treated with antivirals presented with a more severe disease and 57% of them were treated with cyclosporine or infliximab before initiation of gancyclovir,while none of the patients without antivirals required rescue therapy.One patient died and another patient underwent urgent colectomy during hospitalization,both of them from the gancyclovir-treatment group.For the entire follow-up time(13 ± 13 mo),a total of 3 colectomies and one death occurred,all among the antiviral-treated patients(for colectomy:3/7 vs 0/6 patients,P = 0.19;for combined adverse outcome:4/7 vs 0/6 patients,P = 0.07).In 9/13 patients,immunohistochemistry for CMV was performed on biopsies obtained during a subsequent colonoscopy and was positive in one patient only.CONCLUSION:Gancyclovir-treated patients had a more severe disease and outcome,probably unrelated to antiviral therapy.Immunohistochemistry-CMV-positive patients with mild disease may recover without antiviral therapy.     

Anti-inflammatory activity of probiotic Bifidobacterium： Enhancement of IL-10 production in peripheral blood mononuclear cells from ulcerative colitis patients and inhibition of IL-8 secretion in HT-29 cells

AIM： To determine the anti-inflammatory activity of probiotic Bifidobacteria in Bifidobacteria-fermented milk （BFM） which is effective against active ulcerative colitis （UC） and exacerbations of UC, and to explore the immunoregulatory mechanisms. METHODS： Peripheral blood mononuclear cells （PBMNC） from UC patients or HT-29 cells were co-cultured with heat-killed probiotic bacteria or culture supernatant of Bifidobacterium breve strain Yakult （BbrY） or Bifidobacterium bifidum strain Yakult （BbiY） to estimate the amount of IL-10 or IL-8 secreted. RESULTS： Both strains of probiotic Bifidobacteria contained in the BFM induced IL-10 production in PBMNC from UC patients, though BbrY was more effective than BbiY. Conditioned medium （CM） and DNA of both strains inhibited IL-8 secretion in HT-29 cells stimulated with TNF-α, whereas no such effect was observed with heat- killed bacteria. The inhibitory effect of CM derived from BbiY was greater than that of CM derived from BbrY. DNAs of the two strains had a comparable inhibitory activity against the secretion of IL-8. CM of BbiY induced a repression of IL-8 gene expression with a higher expression of IκB-ζ mRNA 4 h after culture of HT-29 cells compared to that in the absence of CM.CONCLUSION： Probiotic Bifidobacterium strains in BFM enhance IL-10 production in PBMNC and inhibit IL-8 secretion in intestinal epithelial cells, suggesting that BFM has anti-inflammatory effects against ulcerative colitis.     

Interleukin-22 ameliorates acute severe pancreatitisassociated lung injury in mice

AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22(r IL-22) on L-arginine-induced acute severe pancreatitis(SAP)-associated lung injury and the possible signaling pathway involved.METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase(MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin(HE) staining. Expression of B cell lymphoma/leukemia-2(Bcl-2), Bcl-x L and IL-22RA1 m RNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group(P 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-x L m RNAs in the SAP group was decreased markedly, while the IL-22RA1 m RNA expression was increased significantly relative to the normal control group(P 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-x L or IL-22RA1 m RNA(P 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the r IL-22 group were significantly lower than those in the SAP group(P 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, r IL-22 stimulated the expression of Bcl-2, Bcl-x L and IL-22RA1 m RNAs in the lung(P 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the r IL-22 group was significantly higher than that in the PBS group(P 0.05).CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.     

Ethnic variations in ulcerative colitis: Experience of an international hospital in Thailand

AIM: To investigate the clinical characteristics, treatment, medication use, and treatment response in patients with ulcerative colitis(UC) across ethnic groups.METHODS: This study retrospectively analyzed medical records of all 268465 patients who visited the Bumrungrad International Digestive Disease Center during 2005-2010. The demographics, clinical characteristics, medication use, results of investigations, and medical and surgical management for patients with UC were evaluated. Evaluation included sigmoidoscopy and colonoscopy performed in compliance with the American Society of Gastrointestinal Endoscopy practice guidelines. Patient ethnicities were categorized into seven groups: Thai, Oriental, South Asian(SA), Middle Eastern(ME), Caucasian, African, and Hispanic. UC pathological severity was classified into inactive, mild, moderate, and severe. Associations between categorical variables were analyzed using the χ2 or Fischer's exact test. Associations between categorical and interval variables were analyzed usingStudent's t-test and/or analysis of covariance.RESULTS: UC was diagnosed in 371 of the 268465 patients: male 56.33%; ME 42%, Caucasian 23%, and Thai 19%. Annual incidence of UC was 82 cases per 100000 with wide ethnic variation, ranging from 29 to 206 cases per 100000 in Oriental and ME patients, respectively. Of the patients with UC, 16.71% had severe UC with highest incidence among the patients from ME(20.39%) and lowest among the Caucasian population(11.90%). ME had highest proportion of pancolitis(52.90%), followed by Caucasian(45.35%) and Asian(34.40%). Only 20.93% of Caucasian patients received steroid, compared with 26.40% and 27.10% of Asian and Middle Eastern, respectively(P = 0.732). Overall, 13.72% of UC patients did not respond to steroid therapy, with non-significantly higher proportions of non-responders among Asian and Middle Eastern patients(15.22% and 15.04%, respectively)(P = 0.781). On average, 5.93% underwent surgical management with ethnic variation, ranging from 0% in African to 18% in SA. Cancer was found in three(Thai, ME, and African) cases(0.82 institution-specific incidence).CONCLUSION: Incidence, symptom duration, pathological severity, clinical manifestations, medication use, treatment response, need for surgical consultation, and cancer incidence of patients with UC potentially vary by ethnicity.     

Th22 cell accumulation is associated with colorectal cancer development

AIM: To investigate the expression of Th22 cells and related cytokines in colorectal cancer(CRC) tissues, and the probably mechanism.METHODS: CRC tumor and paratumor tissues were collected to detect the expression levels of Th22 cells and of related cytokines by immunohistochemistry, flow cytometry and real-time quantitative polymerase chain reaction(RT-q PCR).Interleukin(IL)-22 alone or with a STAT3 inhibitor was co-cultured with RKO cells in vitro to study the effects of IL-22 on colon cancer cells.IL-22 alone or with a STAT3 inhibitor was injected into a BALB/c nude mouse model with subcutaneously transplanted RKO cells to study the effects of IL-22 on colon cancer growth.RESULTS: The percentage of Th22 cells in the CD4+ T subset was significantly higher in tumor tissues compared with that in paratumor tissues(1.47% ± 0.083% vs 1.23% ± 0.077%, P 0.05) as determined by flow cytometry.RT-qP CR analysis revealed that the m RNA expression levels of IL-22, aryl hydrocarbon receptor, CCL20 and CCL22 were significantly higher in tumor tissues compared with those in paratumor tissues.CCL27 mR NA also displayed a higher expression level in tumor tissues compared with that in paratumor tissues; however, these levels were not significantly different(2.58 ± 0.93 vs 2.30 ± 0.78, P 0.05).IL-22 enhanced colon cancer cell proliferation in vitro and displayed anti-apoptotic effects; these effects were blocked by adding a STAT3 inhibitor.IL-22 promoted tumor growth in BALB/c nude mice; however, this effect was reversed by adding a STAT3 inhibitor.CONCLUSION: Th22 cells that accumulate in CRC may be associated with the chemotactic effect of the tumor microenvironment.IL-22 is associated with CRC development, most likely via STAT3 activation.