CTLA4 −1661A/G and 3′UTR long repeat polymorphisms are associated with ulcerative colitis and influence CTLA4 mRNA and protein expression

Chen, Z; Brant, Steven R.; Li, C; Shrestha, Umid Kumar; Jiang, Ting; Zhou, Feng; Jiang, Yi; Shi, Xiaohong; Zhao, Ya-Fei; Li, J; Xia, Bing

doi:10.1038/gene.2010.16

Cited by 22 publications

(12 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Semi-quantitative analysis of staining intensity for the HSF2 protein was performed using the HPIAS-2000 image analysis software (Tongji Qianping Imaging Inc., Wuhan, China) according to Chen [15] and Wang et al [16]. In brief, four highly magnified visual fields (10×40 magnification) (with no overlap) from each tissue section were randomly selected, and theirs digitalized images were submitted to the image analysis software.…”

Section: Methodsmentioning

confidence: 99%

Heat Shock Factor 2 Levels Are Associated with the Severity of Ulcerative Colitis

et al. 2014

View full text Add to dashboard Cite

Background and AimsThe 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.MethodsDifferential 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.ResultsHSF2 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.ConclusionsHSF2 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.

show abstract

Section: Methodsmentioning

confidence: 99%

Heat Shock Factor 2 Levels Are Associated with the Severity of Ulcerative Colitis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…So far, little is known about the IL-23/Th17 pathway in Chinese IBD patients, and many studies illustrate that genetic mutations that predispose to IBD appear to vary between different geographical and racial groups [6, 7]. Thus, our previous study examined the distribution of 26 SNPs of UC and 18 SNPs of CD in the IL-23/Th17 pathway genes in Chinese IBD patients and found that the polymorphisms of IL-12B, IL23R, JAK2, and TNFSF15 are strongly associated with Chinese IBD patients.…”

Section: Introductionmentioning

confidence: 99%

High Intestinal and Systemic Levels of Interleukin-23/T-Helper 17 Pathway in Chinese Patients with Inflammatory Bowel Disease

Song

Zhou

et al. 2013

Mediators of Inflammation

View full text Add to dashboard Cite

Interleukin-23/T-helper 17 (IL-23/Th17) pathway plays a key role in the pathogenesis of inflammatory bowel disease (IBD), but little is known about its expression in Chinese population. In this study, we investigated the mRNA and protein levels of IL-12p40, tumor necrosis factor-like cytokine 1A (TL1A), Janus kinase 2 (JAK2), and IL-23R both locally and systemically in Chinese IBD patients. Our results indicated that the mRNA levels of IL-12p40 and TL1A were increased in ulcerative colitis (UC) patients. Furthermore, serum IL-12p40 and TL1A levels were higher in active UC patients, especially in patients with disease course less than 1.25 years or initial onset. No correlation was found between the genotype and serum levels of IL-12p40 or TL1A in UC patients. Additionally, the mRNA and protein expression of JAK2 and IL-23R were increased in UC and Crohn's disease (CD) patients. Taken together, our results provided evidence that IL-23/Th17 pathway genes may represent important biomarkers of active stage of IBD and serve as novel therapeutic targets for IBD in Chinese population.

show abstract

“…Abatacept, which inhibits T-cell costimulation (CTLA4-Ig), was theorized to be useful in IBD, as CTLA4 polymorphisms may play a role in pathogenesis of the disease [87,88]. However, a Phase 3 study (NCT00406553) among patients with Crohn's Disease was terminated due to lack of efficacy.…”

Section: Treatmentmentioning

confidence: 96%

Inflammatory bowel disease associated arthropathy

Arvikar

Fisher

2011

Curr Rev Musculoskelet Med

View full text Add to dashboard Cite

Arthritis is the most common extraintestinal manifestation of inflammatory bowel disease (IBD) and can have a significant impact on morbidity and quality of life. IBD-associated arthropathy is considered a subtype of seronegative spondyloarthropathy, with axial, peripheral, or a combination of both joint manifestations. Peripheral arthritis is generally non-erosive and the oligoarticular variant particularly may correlate with intestinal disease activity. Axial arthritis may include inflammatory back pain, sacroiliitis, or ankylosing spondylitis, and is less likely to correlate with gastrointestinal symptoms. While there have been advances in identifying predisposing genetic factors and in elucidating pathophysiology of inflammatory bowel disease, the mechanisms surrounding the development of arthritis in IBD remain unclear. Treatment of inflammatory bowel disease is not always sufficient for control of arthritis. While treatment with biologic agents is promising, there remains a great need for larger, randomized studies to address optimal therapy of IBD associated arthropathy.

show abstract

CTLA4 −1661A/G and 3′UTR long repeat polymorphisms are associated with ulcerative colitis and influence CTLA4 mRNA and protein expression

Cited by 22 publications

References 59 publications

Heat Shock Factor 2 Levels Are Associated with the Severity of Ulcerative Colitis

Heat Shock Factor 2 Levels Are Associated with the Severity of Ulcerative Colitis

High Intestinal and Systemic Levels of Interleukin-23/T-Helper 17 Pathway in Chinese Patients with Inflammatory Bowel Disease

Inflammatory bowel disease associated arthropathy

Contact Info

Product

Resources

About