Expression of inflammatory genes in the colon of ulcerative colitis patients varies with activity both at the mRNA and protein level (original) (raw)
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BMC Gastroenterology, 2011
Background: Dysregulation of innate immune response by Toll-Like Receptors (TLRs) is a key feature in Ulcerative Colitis (UC). Most studies have focused on TLR2, TLR3, and TLR4 participation in UC. However, few studies have explored other TLRs. Therefore, the aim of this study was to evaluate the mRNA profiles of TLR1 to 9 in colonic mucosa of UC patients, according to disease activity. Methods: Colonic biopsies were taken from colon during colonoscopy in 51 patients with Ulcerative Colitis and 36 healthy controls. mRNA levels of TLR1 to 9, Tollip, inflammatory cytokines IL6 and TNF were assessed by RT-qPCR with hydrolysis probes. Characterization of TLR9 protein expression was performed by Immunohistochemistry.
The Interleukin-1β (-511T/C) is Associated with Ulcerative Colitis
Iris Publishers LLC, 2018
Purpose: Inflammatory bowel disease (IBD) is a group of illnesses whose primary manifestation is inflammation. The most common typical phenotypes are ulcerative colitis (UC) and Crohn’s disease (CD). Although the precise etiology remains obscure, several reports have indicated that dysfunction of the mucosal immune system play an important role in its pathogenesis. This study aimed to analyzing the genes polymorphisms of immune response in Brazilian patients with IBD. Methods and results: 95 patients were analyzed for the caspase activation and recruitment domains 15/ NOD like receptor 2 (CARD15/NOD2) (rs2066844 and rs2066845), NOD like receptor – (NLRP1) (rs12150220), NLRP3 (rs35829419) and interleukin (IL)-1 (rs16944) genes polymorphisms. The anatomic-clinical form of CD predominant was both, fistulizing and inflammatory each (35.18%), followed by structuring (27.77%) and 1.85% structuring and fistulizing in the same patients. 91 healthy subjects composed the control group. The statistical analysis was performed using R program. NOD like receptor pyrin domain containing 1 and 3 and caspase activation and recruitment domains 15/ NOD like receptor 2 genes R702W and G908R variants were not associated to inflammatory bowel disease susceptibility. We found that AG genotype of interleukin-1beta was associated with the development of UC. Conclusion: Our findings suggest that the IL-1 single nucleotide polymorphism is involved with UC and may be contributing to pathogenesis in Brazilian population.
BMC Gastroenterology, 2009
Background: A definition of disease activity in ulcerative colitis (UC) is difficult. The clinical activity index (CAI) is only an indirect assessment tool of bowel inflammation and the endoscopic activity index (EAI) sometimes cannot reflect the severity of disease to the full extent. Therefore, there is a need for an objective means to quantify inflammatory activity in mucosal biopsies. In our study, we wanted to examine the correlation between transcript levels of interleukin 8 (CXCL8), interferon γ inducible protein 10 (CXCL10), myeloid-related protein 14 (calgranulin B), macrophage inflammatory protein 2 α (CXCL2) with CAI and EAI in UC.
Inflammatory Bowel Diseases, 2013
Clinical trials in ulcerative colitis (UC) rely on certain parameters to evaluate responses that are highly subjective or of low sensitivity. Here, using a select group of genes, we tested the accuracy of gene expression analysis as a biomarker of clinical, endoscopic, and histologic improvements. Intestinal biopsies were obtained from UC patients included in two cohorts. Cohort 1 was used to select for genes whose expression was modulated in active (vs. inactive) UC. Cohort 2 included patients recruited in a phase II study receiving placebo, mesalazine, or dersalazine sodium for 4 weeks. The expression of 44 genes identified in Cohort 1 was assessed at weeks 0 and 4, and was then correlated with biomarkers, as well as with clinical, endoscopic, and histologic scores. Significant changes in the expression of 31 of the 44 genes tested were detected in Cohort 2 at week 4. Gene expression (ΔCt) significantly correlated with the total Mayo score, C-reactive protein (CRP), and fecal calprotectin. The number of genes significantly regulated at week 4 was highly associated with histologic and endoscopic responses. Logistic regression analysis identified four separate genes (IFITM1, ITGB2, IL1R2, IL2RA) whose relative change was independently associated with endoscopic remission with high specificity and sensitivity. Change in the expression of a select set of genes can serve as an early biomarker, one with high specificity and sensitivity to clinical, endoscopic, and histologic responses. This could represent a new tool for identifying early response to treatment in mild to moderately active UC patients.
Scandinavian Journal of Gastroenterology, 2012
Objective. Mucosal cytokine profile determines T cell differentiation and may play an important role in the clinical course of inflammatory bowel disease (IBD). Cytokines from different T helper (Th) cell subsets are elevated in inflamed mucosa of patients with ulcerative colitis (UC), contributing to the inflammation. The aim of this study was to determine the predictive value of pre-treatment mucosal cytokine profile in response to therapy with the anti-TNF agent infliximab (IFX). Material and methods. The expression of Th1, Th17, Th2 and T-regulatory (Treg)-related cytokines was quantified by real-time PCR in mucosal biopsies from 74 UC patients before initiation of IFX induction therapy. Clinical and endoscopic effects were assessed after three infusions. Remission was defined as ulcerative colitis disease activity index (UCDAI) below 3. Results. Higher gene expression levels of IL-17A and IFN-g were significantly associated with remission after three IFX infusions (OR = 5.4, p = 0.013 and OR = 5.5, p = 0.011, respectively). IL-17A and IFN-g mRNA expression showed positive correlation. Th2 and Treg-related mediators were not significantly associated with clinical outcome, but were expressed at higher levels in UC patients compared with the controls. Immunohistochemistry (IHC) confirmed the presence of cells expressing both IL-17A and IFN-g. Conclusions. High expression of Th1-and Th17-related cytokines in the mucosa of UC patients can potentially predict a favorable outcome of IFX induction therapy. Th2 and Treg-related mediators do not appear useful as predictive markers.
Increased Expression of IP-10, IL-8, MCP-1, and MCP-3 in Ulcerative Colitis
The American Journal of Pathology, 1999
Chemokines are thought to be important for the recruitment of granulocytes and mononuclear cells and thus for the maintenance of inflammation in ulcerative colitis (UC). We have studied the expression of interferon-␥ inducible protein-10 (IP-10) , interleukin-8 (IL-8) , monocyte chemoattractant protein (MCP)-1 , MCP-3 , and macrophage inflammatory protein (MIP)-1␣ in UC patients and control individuals to assess the role of these chemokines in disease progression. Colonic biopsies were taken endoscopically from patients and controls , frozen immediately and subsequently stained for IP-10 , IL-8 , MCP-1, MCP-3 , and MIP-1␣ in serial sections. Cells infiltrating the lamina propria but not epithelial cells express the analyzed chemokines. They were differentiated and counted , and chemokine-expressing cells were quantified by image analysis. The percentage of cells expressing IP-10 , IL-8 , MCP-1 , and MCP-3 was significantly enhanced in all UC samples as compared to controls. Expression in the controls was borderline, except for IP-10. No expression of MIP-1␣ was found in controls and UC. IP-10 was also markedly expressed in the mucosa of control biopsies and therefore could have a role in activated T lymphocytes' recruitment into the healthy mucosa.
Journal of Clinical Immunology, 2013
Interleukin (IL)-20, a pro-inflammatory cytokine, is a recently discovered member of the IL-10 family. This cytokine has been described in inflammatory diseases such as psoriasis and asthma. However, IL-20 expression in ulcerative colitis (UC) patients has not been yet described. The aim of this study was to evaluate IL-20 and IL-10 gene and protein expression and their receptors in the mucosa from UC patients. Forty UC patients and 18 non-inflamed controls were studied. IL-10, IL-20, IL-10R1, IL-10R2, IL-20R1 and IL-20R2 gene expression was determined by real time RT-PCR in colonic biopsies. Protein expression was evaluated by immunohistochemistry. Patients in remission had significantly higher IL-10 gene expression in mucosa compared with active patients and controls. Conversely, IL-10R1/B gene expression was decreased in remission compared with active UC patients and controls. IL-20 gene expression was lower in colonic mucosa from UC patients in remission compared with controls and active patients. IL-20R1/B mRNA expression was higher in remission compared with active UC patients and controls. IHQ analysis showed an increased IL-10-, IL-20-, and IL-20R2-producing cells in active UC patients. IL-10-, IL-20-and IL-20R2-expressing epithelial and inflammatory cells were increased in active UC patients, meanwhile IL-20R1 was up-regulated only on inflammatory infiltrates vs. controls. This is the first depiction of the presence of IL-20 and its receptors in UC. Much remains to be learned however, about the pathogenic mechanisms that lead to IBD. This cytokine/receptor imbalance may be implicated in the pathogenesis of UC.
Local and Systemic Liberation of Proinflammatory Cytokines in Ulcerative Colitis
Digestive Diseases and Sciences, 1999
Determination of plasma and tissue cytokinelevels in inflammatory bowel disease have frequentlyresulted in conflicting data. In the present study wedetermined in patients with ulcerative colitis (UC), the levels of the proinflammatory cytokinesinterleukin (IL)-1β, IL-6, interferon(IFN)-γ, and tumor-necrosis factor (TNF)-αliberated by peripheral blood mononuclear cells (PBMC)and lamina propria mononuclear cells (LPMC) after 48-hrculture with pokeweed mitogen (PWM). IL-1β, IL-6,IFN-γ and TNF-α in the supernatant weredetected by ELISA. Results show low basal levels ofIL-1β secretion by PBMC and LPMC, and a considerableincrease after mitogen stimulation. Basal IL-6production by PBMC was higher in UC patients than incontrols [2029 pg/ml, CI9 (–165 to4223) vs 572 pg/ml (–383 to 1527) respectively, P = 0.05] and also afterPWM activation [14,995 pg/ml (7759 -22230) vs 6598 pg/ml(3240-9956), respectively, P = 0.05]. In LPMC, nodifferences in IL-6 secretion were observed. TNF-α in activated PBMC of patients with UC was notsignificantly increased in relation to control (P =0.09). No constitutive secretion of IFN-γ wasobserved in mononuclear cells. IFN-γ levelssecreted by activated LPMC were lower in patients withUC than in controls [1571 pg/ml (–108 to 3251) vs7953 pg/ml (3851-12,055), respectively, P = 0.03]. Theseresults suggest that IL-6, IL-1β, and TNF-α participate as mediators in the inflammatoryphenomena observed in UC. Further studies are necessaryto evaluate the role of IFN-γ in thiscondition.
Gene expression in mononuclear cells from patients with inflammatory bowel disease
Clinical Immunology, 2004
Objectives. Discovery of Nod2 as the inflammatory bowel disease 1 (IBD1) susceptibility gene has brought to light the significance of mononuclear cells in inflammatory bowel disease pathogenesis. The purpose of this study was to examine changes in gene expression in peripheral blood mononuclear cells in patients with untreated Crohn's disease (CD) and ulcerative colitis (UC) as compared to patients with other inflammatory gastrointestinal disorders and to healthy controls. Methods. We used a 2400 gene cDNA glass slide array (MICROMAXk) to examine gene expression in peripheral blood mononuclear cells from seven patients with Crohn's disease, five patients with ulcerative colitis, 10 patients with other inflammatory gastrointestinal disorders, and 22 age-and sex-matched controls. Results. Novel categories of genes differentially expressed in Crohn's disease and ulcerative colitis patients included genes regulating hematopoietic cell differentiation and leukemogenesis, lipid raft-associated signaling, the actin cytoskeleton, and vesicular trafficking. Conclusions. Altered gene expression in mononuclear cells may contribute to inflammatory bowel disease pathogenesis.
Gene expression profile of endoscopically active and inactive ulcerative colitis: preliminary data
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2017
AIM Multiple cytokines and chemokines related to immune response, apoptosis and inflammation have been identified as molecules implicated in ulcerative colitis (UC) pathogenesis. The aim of this study was to identify the differences at gene expression level of a panel of candidate genes in mucosa from patients with active UC (UCA), patients in remission (UCR), and normal controls. PATIENTS, MATERIALS AND METHODS Eleven individuals were enrolled in the study: eight UC patients (four with active lesions, four with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression profile was evaluated by polymerase chain reaction (PCR) array, investigating 84 genes implicated in apoptosis, inflammation, immune response, cellular adhesion, tissue remodeling and mucous secretion. RESULTS Seventeen and three genes out of 84 were found significantly differentially expressed in UCA...