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(1) Background: Developing countries have experienced a rapid recent rise in Inflammatory Bowel Disease (IBD) incidence and emerging evidence suggests processed foods and food additives may predispose one to the development and perpetuation of Crohn’s disease (CD). The aim of this study was to evaluate processed food and food additive intake in CD patients and controls, in Australia (high CD incidence), Hong Kong (intermediate incidence) and mainland China (emerging incidence). (2) Methods: In 274 CD patients (CD), 82 first-degree relatives (FDR), 83 household members (HM) and 92 healthy unrelated controls (HC) from Australia (n = 180), Hong Kong (HK) (n = 160) and mainland China (n = 191) we estimated early life (0–18 years), recent (12 months), and current processed and food additive intake, using validated questionnaires and a 3-day-food diary. (3) Results: Early life processed food intake: Combining all regions, CD were more likely to have consumed soft drinks and fast foods than HM, more likely to have consumed processed fruit and snacks than their FDR, and more likely to have consumed a range of processed foods than HC. HK and China CD patients were more likely to have consumed a range of processed foods than HC. Recent food-additive intake (12-months): Combining all regions, CD patients had significantly higher intakes of aspartame and sucralose, and polysorbate-80, than HC, and more total emulsifiers, artificial sweeteners, and titanium dioxide than FDR and HC. HK and China CD patients had a higher intake of almost all food additives than all controls. Current additive intake (3-days): Australian and HK CD patients had higher total food-additive intake than FDR, and HK CD patients had a higher intake of total food-additives and emulsifiers than HM. (4) Conclusions: CD patients have been exposed to more processed food and food additives than control groups, which may predispose them to CD development and ongoing inflammation.

The intestinal mechanical barrier plays a key role in the pathogenesis of ulcerative colitis (UC). Our previous study showed keratin 1 (KRT1) was downregulated in UC, but the mechanism by which KRT1 affects the intestinal barrier remains unknown. To explore the mechanism of KRT1 in the intestinal barrier in UC. Colonic tissues were collected from 20 UC patients before and after mucosal healing (MH) and 15 healthy controls. The expression of KRT1 was measured by PCR, western blotting and immunohistochemistry (IHC). A dextran sulfate sodium (DSS)-induced colitis model was established in krt1 transgenic (TG) mice, and the mice were treated with methylprednisolone (MP) to explore the role of KRT1 in the intestinal barrier. Inflammation was evaluated through the DAI score, colon, spleen and H&E. The expression of KRT1 and tight junction (TJ) proteins in mouse was analysed by the same methods. The transcription and expression of KRT1 in UC was decreased and recovered after MH but did not reach the level of the healthy controls. Similar to the clinical results, the expression of krt1 was decreased in DSS-induced colitis and upregulated after MP. Moreover, the krt1 TG group exhibited less inflammation than wild-type (WT) group. The expression of Occludin and ZO-1 decreased after DSS induction, the decreases in Occludin and ZO-1 in the krt1 TG group were lower than WT group, which was significantly increased after MP, while the expression of Claudin-2 exhibited the opposite effect. Keratin 1 maintains the intestinal barrier by upregulating TJ proteins in UC.

(1) Background: Developing countries have experienced a rapid recent rise in Inflammatory Bowel Disease (IBD) incidence and emerging evidence suggests processed foods and food additives may predispose one to the development and perpetuation of Crohn’s disease (CD). The aim of this study was to evaluate processed food and food additive intake in CD patients and controls, in Australia (high CD incidence), Hong Kong (intermediate incidence) and mainland China (emerging incidence). (2) Methods: In 274 CD patients (CD), 82 first-degree relatives (FDR), 83 household members (HM) and 92 healthy unrelated controls (HC) from Australia (n = 180), Hong Kong (HK) (n = 160) and mainland China (n = 191) we estimated early life (0–18 years), recent (12 months), and current processed and food additive intake, using validated questionnaires and a 3-day-food diary. (3) Results: Early life processed food intake: Combining all regions, CD were more likely to have consumed soft drinks and fast foods than HM, more likely to have consumed processed fruit and snacks than their FDR, and more likely to have consumed a range of processed foods than HC. HK and China CD patients were more likely to have consumed a range of processed foods than HC. Recent food-additive intake (12-months): Combining all regions, CD patients had significantly higher intakes of aspartame and sucralose, and polysorbate-80, than HC, and more total emulsifiers, artificial sweeteners, and titanium dioxide than FDR and HC. HK and China CD patients had a higher intake of almost all food additives than all controls. Current additive intake (3-days): Australian and HK CD patients had higher total food-additive intake than FDR, and HK CD patients had a higher intake of total food-additives and emulsifiers than HM. (4) Conclusions: CD patients have been exposed to more processed food and food additives than control groups, which may predispose them to CD development and ongoing inflammation.

Objective and backgroundThe overactivation of NLRP3 inflammasome is a critical factor for ulcerative colitis (UC). We found that heat shock transcription factor 2 (HSF2), which is highly expressed in UC, could inhibit the activation of NLRP3 inflammasome and reduce IL-1β in intestinal epithelial cells(IECs), but the mechanisms were still unclear. We aimed to elucidate the mechanisms of HSF2 inhibiting the activation of NLRP3 inflammasome of IECs.Methods: TEM was used to detect the number of damaged mitochondria and the level of mitophagy in intestinal mucosa of UC patients, healthy controls, mice and Caco-2 cells. ROS levels were detected by immunofluorescence or flow cytometry. RT-PCR, WB and immunohistochemistry were used to detect the level of PARL, PINK1 and Parkin.Results: The levels of mitophagy and ROS in intestinal mucosa of UC patients were positively correlated with disease activity. In IECs, after downregulation of HSF2, mitophagy reduced and number of damaged mitochondria and ROS increased, while overexpression of HSF2 showed opposite results. In addition, HSF2 might regulate mitophagy through PARL/PINK1/Parkin signaling pathway.Conclusions:HSF2 may promote mitophagy and decrease the level of mtROS through the PARL/PINK1/Parkin signaling pathway, which might be a potential mechanism of HSF2 inhibiting inflammation in UC.

UC is a chronic inflammatory disease of the colonic mucosa and lacks effective treatments because of unclear pathogenesis. Excessive apoptosis of IECs damages the intestinal epithelial barrier and is involved in the progression of UC, but the mechanism is unknown. HSPs are important in maintaining homeostasis and regulate apoptosis through the mitochondrial pathway. In our previous studies, HSF2, an important regulator of HSPs, was highly expressed in UC patients and negatively correlated with inflammation in mice and IECs. Therefore, we hypothesized that HSF2 may protect against intestinal mucositis by regulating the apoptosis of IECs. In this study, a DSS-induced colitis model of hsf2−/− mice was used to explore the relationship between HSF2 and apoptosis in IECs for the first time. The expression of HSF2 increased in the WT + DSS group compared with that in the WT + H2O group. Moreover, the extent of apoptosis was more severe in the KO + DSS group than in the WT + DSS group. The results showed that HSF2 was negatively correlated with apoptosis in vivo. The expression of HSF2 in Caco-2 cells was changed by lentiviral transfection, and the expression of Bax, cytoplasmic Cyto-C, Cleaved Caspase-9 and Cleaved Caspase-3 were negatively correlated with the different levels of HSF2. These results suggest that HSF2 negatively regulates apoptosis of IECs through the mitochondrial pathway. This may be one of the potential mechanisms to explain the protective role of HSF2 in UC.

Background Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease (IBD), the occurrence of which has been increasing worldwide. Although IBD is an intensively studied human microbiome-associated disease, research on Chinese populations remains relatively limited, particularly on the mucosal microbiome. The present study aimed to analyze the changes in the mucosal microbiome associated with UC from the perspectives of medical ecology and complex network analysis. Results In total, 56 mucosal microbiome samples were collected from 28 Chinese UC patients and their healthy family partners, followed by amplicon sequencing. Based on sequencing data, we analyzed species diversity, shared species, and inter-species interactions at the whole community, main phyla, and core/periphery species levels. We identified four opportunistic “pathogens” (i.e., Clostridium tertium, Odoribacter splanchnicus, Ruminococcus gnavus, and Flavonifractor plautii) with potential significance for the diagnosis and treatment of UC, which were inhibited in healthy individuals, but unrestricted in the UC patients. In addition, we also discovered in this study: (i) The positive-to-negative links (P/N) ratio, which measures the balance of species interactions or inhibition effects in microbiome networks, was significantly higher in UC patients, indicating loss of inhibition against potentially opportunistic “pathogens” associated with dysbiosis. (ii) Previous studies have reported conflicting evidence regarding species diversity and composition between UC patients and healthy controls. Here, significant differences were found at the major phylum and core/periphery scales, but not at the whole community level. Thus, we argue that the paradoxical results found in existing studies are due to the scale effect. Conclusions Our results reveal changes in the ecology and network structure of the gut mucosal microbiome that might be associated with UC, and these changes might provide potential therapeutic mechanisms of UC. The four opportunistic pathogens that were identified in the present study deserve further investigation in future studies.

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Obesity and type 2 diabetes mellitus (T2DM) are associated with changes in the gut bacterial composition, but little is known about the role of the viral community (virome) in disease development. This study aims to characterize the gut virome alterations in obese subjects with or without T2DM.There were 128 obese subjects (body mass index ≥28 kg/mObese subjects, especially those with T2DM (ObT2), had a decreased gut viral richness and diversity compared with lean controls in the Hong Kong cohort (P.05), while no significant differences were observed in the Kunming cohort. Eleven viruses, including Escherichia phage, Geobacillus phage, and Lactobacillus phage were enriched in obese subjects (q.1). Besides, 17 differentially abundant viruses were identified between ObT2 and lean controls (q.1). Further ecologic analysis revealed that intensive transkingdom correlations between viruses and bacteria observed in lean controls were significantly decreased in ObT2 subjects (P.001).Obesity is characterized by altered viral taxonomic composition and weakened viral-bacterial correlations compared with lean controls. Obesity accompanied with T2DM may aggravate the obesity-associated virus signatures, signifying that the gut virome may play an important role in the development of obesity and T2DM. Geographic factors also contributed to the variations of gut virome in obesity and T2DM.

Background: Mucosal healing(MH) is a treatment goal in ulcerative colitis (UC). Our previous studies showed heat shock transcription factor 2 (HSF2) was positively correlated with the activity of U...

Ulcerative colitis (UC) is a chronic inflammatory disease with unknown aetiology. As a pro-inflammatory cytokine, interleukin-1β (IL-1β) plays a critical, damaging role in UC. Heat shock proteins (HSPs) are important anti-inflammatory factors that maintain intestinal epithelial cells (IECs) homeostasis. Heat shock transcription factor 2 (HSF2) is an important regulator of HSPs. In our previous research, we found that HSF2 is highly expressed in UC, is negatively related to colon inflammation of mice, and inhibits the expression of IL-1β, but the specific mechanism is still unclear. As a product of the NLRP3 inflammasome, the expression of IL-1β is closely related to NLRP3 inflammasome activation. Therefore, we hypothesised that HSF2 affects the secretion of IL-1β by regulating activation of the NLRP3 inflammasome. In this study, hsf-/- DSS model mice showed highest levels of expression of the NLRP3 inflammasome and the secretion of IL-1β. In Caco-2 cells, the levels of expression of the NLRP3 inflammasome and the secretion of IL-1β were inhibited by overexpression of HSF2, and inhibited HSF2 increased activation of the NLRP3 inflammasome and the secretion of IL-1β. These findings indicated that HSF2 might be an important target for inflammatory modulation in UC.

Bacterial DNA (bacDNA) is frequently found in serum of patient with ulcerative colitis (UC) and Crohns disease, even blood bacterial culture is negative. How bacDNA evades immune elimination and is translocated into blood remain unclear. Here, we showed that bacDNA avoids elimination and disables bacteria-killing function of antimicrobial peptide LL-37 (Cramp in mice) by forming complex with LL-37, which is inducible after culture with bacteria or bacterial products. Elevated LL-37-bacDNA complex was found in plasma and lesions of patients with UC. LL-37-bacDNA promoted inflammation by inducing Th1, Th2 and Th17 differentiation and activating toll-like receptor-9 (TLR9). The complex also increased paracellular permeability, which possibly combines its inflammatory effects to promote local damage and bacDNA translocation into blood. Cramp-bacDNA aggravated mouse colitis severity while interference with the complex ameliorated the disease. The study identifies that inflammatogenic bacDNA utilizes LL-37 as a vehicle for blood translocation and to evade immune elimination. Additionally, bacteria may make a milieu by releasing bacDNA to utilize and resist host antimicrobial peptides as a trojan horse.

Background In our previous study, we found that fecal heat shock transcription factor 2 (HSF2) concentration may be an evaluation index for predicting the mucosal healing of Ulcerative Colitis (UC). So this study is aiming to explore the mechanism of HSF2 in the mucosal repair of UC. Methods The DAI, colon damage score and histopathology score were recorded in DSS induced colitis. The transcription and expression level of HSF2 and TGF-β in the mice colon tissue were detected by PCR and immunohistochemistry. HSF2 levels in HT-29 cells was manipulated by RNA interference and plasmids transfection. The concentrations of IL-1β, TNF-α and TGF-β in cells supernatant were detected by ELISA after induced by LPS. The phosphorylation level of ERK, P38, JNK and Smad2/3 were detected by Western Blot. Results The DAI, colon damage and pathology score of methylprednisolone(MP)treatment group were lower than DSS model group (figure 1). The transcription and expression of HSF2 and TGF-β in colon mucosal tissue were increased and decreased synchronously in DSS model group and MP treatment group(figure 2). The phosphorylation level of ERK, P38 and JNK increased significantly in HSF2 siRNA compared with the negative control group. The concentrations of IL-1β and TNF- α in the supernatant of HT-29 cells increased in HSF2 siRNA group. On the contrary, the phosphorylation level of ERK, P38 and JNK decreased significantly in HSF2-FLAG plasmid transfection compared with the Blank Vector group. The concentrations of IL-1β and TNF- α in the supernatant of HT-29 cells reduced (figure 3, figure 4). The phosphorylation level of Smad2/3 decreased in HSF2 siRNA compared with the negative control group. The concentrations of TGF-β in the supernatant of HT-29 cells reduced in HSF2 siRNA group. On the contrary, the phosphorylation level of Smad2/3 increased significantly in HSF2-FLAG plasmid transfection compared with the Blank Vector group. The concentrations of TGF-β in the supernatant of HT-29 cells increased (Figure 4). Conclusions HSF2 can promote the mucosal repair of ulcerative colitis by inhibiting the inflammatory response and promoting mucosal repair factor expression.

Background & Aims Beyond bacteria, the human gastrointestinal tract is host to a vast diversity of fungi, collectively known as the gut mycobiome. Little is known of the impact of geography, ethnicity, and urbanization on the gut mycobiome at a large population level. We aim to delineate the variation of human gut mycobiome and its association with host factors, environmental factors, and diets. Methods Using shotgun metagenomic sequencing, we profiled and compared the fecal mycobiome of 942 healthy individuals across different geographic regions in China (Hong Kong and Yunnan), spanning 6 ethnicities: Han, Zang, Bai, Hani, Dai, and Miao (including both urban and rural residents of each ethnicity). In parallel to fecal sampling, we collected participant metadata (environmental exposure, bowel habits, anthropometrics, and medication), diet, and clinical blood measurement results (a total of 118 variables) and investigated their impact on the gut mycobiome variation in humans. Results The human gut mycobiome was highly variable across populations. Urbanization-related factors had the strongest impact on gut mycobiome variation, followed by geography, dietary habit, and ethnicity. The Hong Kong population (highly urbanized) had a significantly lower fungal richness compared with Yunnan population. Saccharomyces cerevisiae was highly enriched in urban compared with rural populations and showed significant inverse correlations with liver pathology–associated blood parameters, including aspartate transaminase, alanine transaminase, gamma-glutamyltransferase, and direct bilirubin. Candida dubliniensis, which was decreased in urban relative to rural populations, showed correlations with host metabolism-related parameters in blood, including a positive correlation with fasting high-density lipoprotein cholesterol levels and a negative correlation with fasting glucose levels. The fungal-blood parameter correlations were highly geography- and ethnicity-specific. Food choices had differential influences on gut mycobiome and bacterial microbiome, where taxa from the same genus tended to be coregulated by food and thereby cobloom. Ethnicity-specific fungal signatures were associated with distinct habitual foods in each ethnic group. Conclusions Our data highlight, for the first time to our knowledge, that geography, urbanization, ethnicity, and habitual diet play an important role in shaping the gut mycobiome composition. Gut fungal configurations in combination with population characteristics (such as residing region, ethnicity, diet, lifestyle) influence host metabolism and health.

Butyrate-induced autophagy and anti-inflammatory effects of IECs plays an important role in UC. HSP has been proved to be associated with autophagy. HSF2, as an important regulator of HSP, has been determined to be highly expressed in UC. This study was designed to elucidate the relationship between HSF2, butyrate and epithelial autophagy and the potential mechanism of HSF2-related autophagy in UC. The autophagy levels and HSF2 expression in intestinal mucosa were increased in UC patients compared to controls. In DSS colitis models, hsf2-/- mice exhibited more severe intestinal inflammation and lower autophagy levels than wild-type mice. HSF2 expression could be induced by sodium butyrate and LPS as a dose-response relationship in HT-29 cells, epigenetically via increasing histone acetylation levels at the promoter region by sodium butyrate. Autophagy induced by sodium butyrate was promoted by overexpression HSF2 in HT-29 cells. Moreover, overexpression HSF2 decreased the expression and phosphorylation levels of PI3K, Akt and mTOR induced by sodium butyrate. HSF2 might induced by sodium butyrate and inflammation and played protective roles in UC by enhancing autophagy of IECs. This indicated that HSF2 may be a critical target for autophagy modulation and a new potential therapeutic target in UC.

Background In our previous study, we found that Heat Shock transcription Factor 2 (HSF2) was differentially expressed in Ulcerative Colitis (UC) patients and increased in parallel with the severity of UC. So this study is aiming at providing a new noninvasive index for predicting the mucosal healing of UC. Methods Faecal samples were collected from 51 UC with MES (0,1,2,3) and health controls. The concentration of feacl HSF2 was detected by Elisa. The correlation between faecal HSF2 levels and MES was compared by Pearson correlation analysis. A total of 231 follow-up UC patients were included. The faecal samples were collected in the early morning, and colonoscopy was performed in the next day for MES scoring. MES. Results The concentration of faecal HSF2 in the normal control group and UC patients with MES=0,1,2,3 were (0.64±0.09, 1.30±0.35, 1.84±0.46,2.38±0.57,3.38±0.42) ng/ml respectively. The level of faecal HSF2 was a positive correlation with MES (r=0.81). The concentration of faecal HSF2 was increasing in the group of UC patients with MES=0,1,2,3 compared with the normal control group. The sensitivity, specificity, positive and negative predictive value of faecal HSF2 to predict mucosal healing was (67.8%,80.9%,67.1% and 81.5%) respectively. The clinical value of specificity and the negative predictive value was better than sensitivity and positive predictive value. The AUC of faecal HSF2 to predict mucosal healing was 0.919 (95% CI:0.846–0.992, p Conclusions Faecal HSF2 concentration may be used as a high accuracy noninvasive evaluation index for predicting the mucosal healing of UC.

Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn’s disease (CD). Glucocorticoids (GCs) are the most effective treatment for moderate to severe active UC. However, one-third of patients are not sensitive to GCs (i.e., they are GC resistant). The mechanism of GC resistance in IBD is unknown, and it remains unclear how to predict resistance in IBD patients. This study aimed to explore the possible correlation between miRNA expression and variability in GC-resistant and GC-sensitive patients with ulcerative colitis. A comparative serum microRNA analysis in GC-resistant and GC-sensitive patients with ulcerative colitis was conducted by microarray. Differential microRNA expression was further validated in serum samples by quantitative real-time PCR. We found that downregulated microRNAs had a significant correlation with several signal transduction pathways (the PI3K-Akt and MAPK signaling pathways) and target genes (HSP90B1, MAPK13, MAPK9, PIK3AP1 and TLR4) related to GC resistance. Eight downregulated microRNAs were chosen for further validation in 76 serum samples. The results showed that miR-16-2-3p, miR-30e-3p, miR-32-5p, miR-642a-5p, miR-150-5p, and miR-224-5p were significantly downregulated in the GC-resistant group. Receiver operating characteristic analysis showed that the area under the curves (AUCs) for those microRNAs were 0.94, 0.93, 0.85, 0.87, 0.92, and 0.99, with specificities of 97.30%, 89.20%, 59.50%, 73.00%, 97.30%, and 97.30% and sensitivities of 74.40%, 84.60%, 97.40%, 92.30%, 66.70%, and 89.70%, respectively. Our study provides preliminary evidence for the pathogenic mechanism of GC resistance and shows that serum microRNAs might serve as biomarkers for GC resistance in IBD.

Inflammatory bowel disease (IBD) is the result of a chronic intestinal inflammatory response which usually occurred in colon and small intestine. Keratins constitute the intermediate filament cytoskeleton in all epithelia. The present study was intended to explore the role of Keratin 1 (KRT1) in the progress of IBD. In normal intestinal tissue, the expression of KRT1 was detected by RT-PCR and Western blot. The levels of KRT1 protein significantly decreased in serum samples of IBD patients as compared with sera of healthy controls. Immunohistochemistry revealed that the expression of KRT1 decreased in various intestinal diseases, especially in Crohn's disease and ulcerative colitis. Furthermore, down-regulated KRT1 was correlated with the severity of IBD. The overexpression of KRT1 maintained epithelial barrier in Caco-2 cells after IL-1β treatment. Furthermore, IL-1β-induced disruption of tight junction became significantly attenuated in KRT1 over-expressing Caco-2 cells as compared with control cells. Thus, KRT1 played an important role of maintaining epithelial barrier and its down-regulation in intestinal tissue was correlated with the progression of IBD.

The transmembrane receptor guanylate cyclase-C (GC-C) signaling pathway has been implicated in several gastrointestinal disorders. Activation of GC-C via guanylin (Gn) and uroguanylin (Ugn) regulates intestinal fluid and electrolyte homeostasis. However, how it regulates the pathogenesis of inflammatory bowel disease (IBD) is still unclear. Here, we investigated the activation of GC-C signaling in ulcerative colitis (UC) of different clinical severities. A total of 60 UC patients and 20 normal controls were recruited. Evaluation of the UC disease activity index (DAI) was performed using a modified Mayo scoring system. The expression of GC-C, Gn and Ugn in the colonic mucosa was measured by quantitative real-time PCR and Western blot. We found that the UC patients had significantly lower expression of GC-C, Gn and Ugn than the controls. Furthermore, there were significant differences for GC-C, Gn and Ugn expression for the UC groups of Grade 1, 2 and 3 and their expression levels were reduced with increases in their DAI. Taken together, our results demonstrate that GC-C, Gn and Ugn are downregulated in UC and this downregulation is more significant with aggravation of the clinical condition. Therefore, the GC-C signaling pathway may be implicated in the progression of UC.

Background The aim of this study was to examine environmental factors associated with inflammatory bowel disease (IBD) in Yunnan Province, a southwestern highland region of China. Methods In this nested case-control study, newly diagnosed ulcerative colitis (UC) cases in 2 cities in Yunnan Province and Crohn’s disease (CD) cases in 16 cities in Yunnan Province were recruited between 2008 and 2013. Controls were matched by geography, sex and age at a ratio of 1:4. Data were collected using the designed questionnaire. Conditional logistic regression models were used to estimate adjusted odds ratios (ORs). Results A total of 678 UC and 102 CD cases were recruited. For UC, various factors were associated with an increased risk of developing UC: dietary habits, including frequent irregular meal times; consumption of fried foods, salty foods and frozen dinners; childhood factors, including intestinal infectious diseases and frequent use of antibiotics; and other factors, such as mental labor, high work stress, use of non-aspirin non-steroidal anti-inflammatory drugs and allergies (OR > 1, p < 0.05). Other factors showed a protective effect: such as consumption of fruits, current smoking, physical activity, and drinking tea (OR < 1, p < 0.05). For CD, appendectomy and irregular meal times increased the disease risk (OR >1, p < 0.05), whereas physical activity may have reduced this risk (OR < 1, p < 0.05). Conclusions This study is the first nested case-control study to analyze the association between environmental factors and IBD onset in a southwestern highland region of China. Certain dietary habits, lifestyles, allergies and childhood factors may play important roles in IBD, particularly UC.

Background and aims The morbidity of ulcerative colitis (UC) is increasing in China every year. In addition, there is a lack of accurate diagnostic indices with which to evaluate the activity of the disease. The aim of this study was to identify UC-associated proteins as biomarkers for the diagnosis, and objective assessment of disease activity. Methods Differential expression of serum proteins from UC patients compared to normal controls was analyzed by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS). The expression of heat shock factor 2(HSF2)in colonic mucosa in Crohn's disease, Behcet's disease, ulcerative colitis, intestinal tuberculosis, infective enteritis, intestinal lymphoma, and normal controls was investigated by immunohistochemistry (IHC). The expression of the HSF2 in colonic mucosa of UC subjects with varying severity of disease was measured by real time-PCR and Western Blots. The expression of HSF2 was inhibited by HSF2 small interfering RNA (siRNA) transfection in Caco-2 cells. The concentrations of HSF2, IL-1β, and TNF-α in serum and IL-1β, and TNF-α in the supernatants of transfected Caco-2 cells were determined by ELISA. Results HSF2 was differentially expressed in UC patients compared to normal controls. HSF2 expression was significantly higher in the intestinal mucosa of UC patients compared to other six groups. The results of immunohistochemistry, real time-PCR, Western Blots, and ELISA showed that the expression of HSF2 increased in parallel with the severity of UC. The serum concentration of HSF2 also positively correlated with levels of IL-1β and TNF-α. After down-regulation expression of HSF2 in Caco-2 cells by RNA interference, the productions of IL-1β and TNF-α stimulated by lipopolysaccharide (LPS) increased dramatically. Conclusions HSF2 appears to be a potential novel molecular marker for UC activity, and may provide a basis for studies on the pathogenesis and novel therapeutic targets for UC.