Human neutrophil peptides 1–3 are useful biomarkers in patients with active ulcerative colitis

Kanmura, Shuji; Uto, Hirofumi; Numata, Masatsugu; Hashimoto, Shinichi; Moriuchi, Akihiro; Fujita, Hiroshi; Oketani, Makoto; Ido, Akio; Kodama, Mayumi; H, Ohi; Tsubouchi, Hirohito

doi:10.1002/ibd.20854

Cited by 42 publications

(64 citation statements)

References 34 publications

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“…Patients harboring PSD methylation could escape from severe inflammation because of insufficient host response to inflammation, such as neutrophil-induced apoptosis, leading to long-term, persistent inflammation without an appropriate host response. Our findings are congruent with those reported by Kanmura et al, who showed that the levels of neutrophil peptide were significantly higher in patients with active UC than in patients whose UC was in remission and tended to be higher than those in patients with colon cancer (46). UC-associated colorectal cancer progresses from areas of dysplastic mucosa (47,48) unlike sporadic colorectal cancer (49), which arises from adenomatous polyps.…”

Section: Discussionsupporting

confidence: 92%

Aberrant methylation of the Pleckstrin and Sec7 domain-containing gene is implicated in ulcerative colitis-associated carcinogenesis through its inhibitory effect on apoptosis

Suzuki¹

2011

Int J Oncol

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Abstract. The Pleckstrin and Sec7 domain-containing (PSD)gene, which regulates skeletal rearrangements, has been found to be more frequently methylated both in ulcerative colitis (UC)-associated colorectal cancer tissues (5 of 7; 71.4%) and matched normal epithelia (4 of 7; 57.1%) compared to nonneoplastic UC epithelia (6 of 22; 27.3%) and sporadic colorectal cancer tissues (6 of 32; 18.8%). The levels of PSD mRNA were positively correlated with the methylation status of PSD, as shown by both MSP and bisulfite sequencing. To determine the potential role of PSD silencing in the mechanisms underlying UC-associated carcinogenesis, the levels of senescence, proliferation and apoptosis were evaluated in a normal human fibroblast cell line (NHDF) in which 93% of PSD expression was knocked down by a small-interfering RNA (si-RNA). Although there were no significant differences in the levels of senescence and proliferation caused by PSD knockdown, the level of apoptosis was significantly decreased by PSD knockdown (5.3% in siControl-treated cells vs. 0.67% in siPSD-treated cells, p=0.0001). In addition, reactive oxygen species inducers accelerated apoptosis in NHDF and a neutrophil-like cell line, which was significantly reduced by PSD knockdown. To verify the effect of PSD methylation in tissue sections including 21 samples from UC patients with or without tumors, we elucidated PSD promoting accumulation of filamentous-actin (F-actin) and apoptosis by immunohistochemistry and TUNEL assay, respectively. Both levels of accumulation of F-actin and apoptosis were significantly decreased in specimens from UC patients with PSD methylation compared to those without PSD methylation (F-actin: 0.69±0.86 with vs. 1.57±0.51 without, p=0.0031, apoptotic index: 0.31±0.63 with vs. 1.0±0.88 without, p=0.0277). In conclusion, our results indicate that PSD methylation plays a significant role in the mechanisms underlying UC-associated carcinogenesis through its inhibitory effect on apoptosis in the interaction between colorectal mucosa and neutrophils.

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Section: Discussionsupporting

confidence: 92%

Aberrant methylation of the Pleckstrin and Sec7 domain-containing gene is implicated in ulcerative colitis-associated carcinogenesis through its inhibitory effect on apoptosis

Suzuki¹

2011

Int J Oncol

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“…Han et al [34] identified 16 additional proteins that were expressed differently between active and inactive CD. Kanmura et al [23] asso ciated a higher level of HNP 13 with a positive response following induction of corticosteroid therapy, whilst non responders had lower HNP 13 levels. Meuwis et al [37] published a second report which identified a serum protein profile which correlated with infliximab response.…”

Section: Pre-clinical Presentationmentioning

confidence: 99%

“…From the protein spectra detected, platelet factor 4, myeloid related protein 8, fibrinopeptide A and haptoglobin α2 were considered diagnostically important. Kanmura et al [23] examined UC serum samples using SELDITOF MS and identified that human neutrophil peptide (HNP) 13 was differenti ally expressed. HNP 13 was confirmed by ELISA to differentiate active UC from inactive UC, all CD cases and controls, but not colorectal cancer.…”

Section: Biomarker Discovery Studiesmentioning

confidence: 99%

“…Healthy controls: 30 Kanmura et al [23] Blood CD: 22 SELDI-TOF Plasma concentrations of HNP1, 2 and 3 were significantly higher in active UC compared to inactive UC, CD and control patients UC: 48 Colorectal Cancer: 5 Infectious colitis: 6 Healthy controls: 13 Hatsugai et al [24] Blood CD: 13 2-DE Multivariate analysis of peripheral blood mononuclear cells protein profile 58 protein) allowed for accurate discrimination between UC and CD UC: 17 MALDI-TOF Healthy controls: 17 Nanni et al [25] Blood…”

Section: Uc: 30 Inflammatory Control: 30mentioning

confidence: 99%

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Current application of proteomics in biomarker discovery for inflammatory bowel disease

Chan¹,

Wasinger²,

Leong³

2016

WJGP

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Recently, the field of proteomics has rapidly expanded in its application towards clinical research with objectives ranging from elucidating disease pathogenesis to discovering clinical biomarkers. As proteins govern and/or reflect underlying cellular processes, the study of proteomics provides an attractive avenue for research as it allows for the rapid identification of protein profiles in a biological sample. Inflammatory bowel disease (IBD) encompasses several heterogeneous and chronic conditions of the gastrointestinal tract. Proteomic technology provides a powerful means of addressing major challenges in IBD today, especially for identifying biomarkers to improve its diagnosis and management. This review will examine the current state of IBD proteomics research and its use in biomarker research. Furthermore, we also discuss the challenges of translating proteomic research into clinically relevant tools. The potential application of this growing field is enormous and is likely to provide significant insights towards improving our future understanding and management of IBD.

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“…We have shown that plasma concentrations of HNP 1-3 in patients with active UC were significantly higher than those in healthy subjects or patients with inactive UC, CD, or infectious enterocolitis, which may reflect the infiltration and activation of neutrophils in the intestinal mucosa of patients with active UC. Thus, HNP 1-3 are novel biomarkers for assessing UC disease activity and therapeutic response [11] . However, there are no data on HNP 1-3 levels in the stools of patients with IBD, and whether HNP 1-3 are candidate fecal markers of intestinal inflammation.…”

mentioning

confidence: 99%

Fecal Human Neutrophil Peptide Levels Correlate with Intestinal Inflammation in Ulcerative Colitis

et al. 2016

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Background/Aim: Fecal markers have recently been found to provide convenient and noninvasive assessment of intestinal inflammation in inflammatory bowel disease (IBD). In this study, we examined the clinical significance of fecal human neutrophil peptides (F-HNP) in the evaluation of IBD disease activity. Methods: This study enrolled 70 patients with IBD, consisting of 45 patients with ulcerative colitis (UC), 25 patients with Crohn's disease (CD), and 11 non-IBD controls. Stools samples were evaluated for the association between F-HNP concentration and disease and endoscopic activity in each group and the correlation between F-HNP and fecal calprotectin (F-CP) concentrations. Results: Median F-HNP levels were as follows: UC: 25.6 ng/ml; CD: 20.1 ng/ml; and non-IBD controls: 4.9 ng/ml. F-HNP levels were significantly higher in each IBD group, especially in the UC group, than in the control group. In the UC group, both F-HNP and F-CP levels were significantly higher during active disease compared to the remission phase. Both markers were significantly correlated with the Mayo endoscopic score, although the correlation was stronger for F-HNP than for F-CP (r = 0.66 vs. r = 0.54). Conclusion: F-HNP is a noninvasive marker that is useful for evaluating UC endoscopic activity.

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Human neutrophil peptides 1–3 are useful biomarkers in patients with active ulcerative colitis

Abstract: HNP 1-3 is a novel biomarker that may be useful for diagnosing patients with active UC and predicting treatment outcomes.

Cited by 42 publications

References 34 publications

Aberrant methylation of the Pleckstrin and Sec7 domain-containing gene is implicated in ulcerative colitis-associated carcinogenesis through its inhibitory effect on apoptosis

Aberrant methylation of the Pleckstrin and Sec7 domain-containing gene is implicated in ulcerative colitis-associated carcinogenesis through its inhibitory effect on apoptosis

Current application of proteomics in biomarker discovery for inflammatory bowel disease

Fecal Human Neutrophil Peptide Levels Correlate with Intestinal Inflammation in Ulcerative Colitis

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