Macrophage migration inhibitory factor in the sera and at the colonic mucosa in patients with ulcerative colitis: clinical implications and pathogenic significance

Murakami, Hidehiro; Akbar, Sk. Md. Fazle; Matsui, Hidetaka; Onji, Morikazu

doi:10.1046/j.1365-2362.2001.00796.x

Cited by 67 publications

(59 citation statements)

References 17 publications

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“…In addition, UC samples used in this study did not show detectable p53 serine 46 phosphorylation, a modification involved in p53-mediated apoptosis (40). Because macrophage migration inhibitory factor (MIF) can inhibit p53-mediated apoptosis (41,42), possibly through PGE-2 production by COX-2 (41,43), and levels of MIF are increased in UC when compared with normal colon samples (44,45), free radical-damaged cells could escape apoptosis and clonally expand. In addition, NO can further attenuate apoptosis by directly inhibiting caspases via nitrosylation (46,47).…”

Section: Discussionmentioning

confidence: 87%

Nitric oxide-induced cellular stress and p53 activation in chronic inflammation

Hofseth

Saito

Hussain

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

326

238

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Free radical-induced cellular stress contributes to cancer during chronic inflammation. Here, we investigated mechanisms of p53 activation by the free radical, NO. NO from donor drugs induced both ataxia-telangiectasia mutated (ATM)-and ataxiatelangiectasia mutated and Rad3-related-dependent p53 posttranslational modifications, leading to an increase in p53 transcriptional targets and a G2͞M cell cycle checkpoint. Such modifications were also identified in cells cocultured with NO-releasing macrophages. In noncancerous colon tissues from patients with ulcerative colitis (a cancer-prone chronic inflammatory disease), inducible NO synthase protein levels were positively correlated with p53 serine 15 phosphorylation levels. Immunostaining of HDM-2 and p21 WAF1 was consistent with transcriptionally active p53. Our study highlights a pivotal role of NO in the induction of cellular stress and the activation of a p53 response pathway during chronic inflammation.posttranslational modification ͉ phosphorylation

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Section: Discussionmentioning

confidence: 87%

Nitric oxide-induced cellular stress and p53 activation in chronic inflammation

Hofseth

Saito

Hussain

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

326

238

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“…Mechanisms involved include activation of the MAP kinase pathways through CD74 and CD44 (Shi et al, 2006), suppression of p53 (Hudson et al, 1999;Fingerle-Rowson et al, 2003) and downregulation of NKG2D enhancing immune evasion by cancer cells (Krockenberger et al, 2008). As with HNPs 1 -3, MIF may lack specificity for gastric cancer as it has been reported as elevated in the plasma of patients with ulcerative colitis and Crohn's disease (de Jong et al, 2001;Murakami et al, 2001). However, preliminary work in our laboratory suggests a degree of disease specificity: serum MIF is also elevated in European patients with hepatocellular carcinoma (relative to our 29 Japanese noncancer controls), but is not elevated in patients with lung or pancreas cancer or individuals without cancer (n X 30 per group, data not shown).…”

Section: Discussionmentioning

confidence: 99%

Identification of macrophage migration inhibitory factor and human neutrophil peptides 1–3 as potential biomarkers for gastric cancer

Mohri

Wei

et al. 2009

Br J Cancer

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BACKGROUND: Proteomic methods have the potential to meet the urgent need for better cancer biomarkers. We have used a range of proteomic analyses of serum and tissue from gastric cancer patients and relevant controls to discover biomarkers for gastric cancer. METHODS: Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI) and antibody arrays were used to compare protein expression in 21 pairs of gastric cancer tissue and adjacent normal mucosa and serum from 51 gastric cancer patients and 29 patients with benign gastric diseases. Expression differences were confirmed by enzyme-linked immunosorbent assay. RESULTS: Tissue analysis shows human neutrophil peptides 1 -3 (HNPs 1 -3) elevated 10-fold (P ¼ 0.001) in gastric cancer relative to adjacent normal mucosa. Macrophage migration inhibitory factor (MIF) was increased five-fold (P ¼ 1.84 Â 10 À7 ) in the serum of gastric cancer patients relative to individuals with benign gastric disease. The large increase in MIF concentration in serum gives an area under the receiver operating characteristic curve of 0.85. CONCLUSIONS: Proteomic analyses of serum and tissue indicate that HNPs 1 -3 and MIF have potential as biomarkers for gastric cancer. In particular MIF may be useful, either alone or in combination with other markers, for diagnosing and monitoring gastric cancer.

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“…The expression of MIF was increased in DSS-induced colitis and administration of anti-MIF antibody significantly improved the DSS-induced symptoms [115]. Moreover, the levels of MIF in the sera of UC patients were significantly higher [116], which suggests that anti-MIF therapy may be a new therapeutic approach in IBD. Since increased MIF-expression is also associated with tumorigenesis [117], it is tempting to speculate that inhibition of MIF may also reduce the risk of colon cancer related to chronic inflammation.…”

Section: Immune Dysregulationmentioning

confidence: 94%

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Gyires¹,

Tóth²,

Zádori

2014

CPD

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Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The two main forms of IBD are Crohn's disease and ulcerative colitis. According to the recent concept the disease is caused by a combination of factors, including genetics, immune dysregulation, barrier dysfunction and the change in microbial flora. Environmental factors, such as changes in diet, antibiotic use, smoking or improved domestic hygiene (e.g. eradication of intestinal helminths) probably contribute to the development and increased prevalence of IBD. Dysregulation of mucosal immunity in IBD causes an overproduction of inflammatory cytokines which resulted in uncontrolled intestinal inflammation. Based on extensive research over the last decade, besides the conventional therapy, there are several novel pathways and specific targets, on which focus new therapeutics. New therapeutics aim 1./ to correct genetic susceptibility by stimulating NOD2 expression, TLR3 signaling or inhibition of TLR4 pathway, 2./ to restore the immune dysregulation by inhibition of pro-inflammatory cytokines (TNF-, IL-6, IL-13, IL-17, IL-18, IL-21), Th1 polarisation (IL-2, IL-12, IL-23, IFN-), T-cell activation, leukocyte adhesion, as well as by immunostimulation (GM-CSF, G-CSF) and anti-inflammatory cytokines (IL-10, IL-11, IFN--1a), 3./ to restore mucosal barrier function and stimulate mucosal healing by different growth factors, such as GH, EGF, KGF, TGF-, VEGF, 4./ to restore the normal bacterial flora by antibiotics, probiotics. However, in spite of these numerous potential targets, the true value and clinical significance of most of the new biologics and molecules are not clear yet.

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Macrophage migration inhibitory factor in the sera and at the colonic mucosa in patients with ulcerative colitis: clinical implications and pathogenic significance

Abstract: These data suggest a role of MIF in the pathogenesis of UC. MIF may be used as a marker of disease activity in UC and control of MIF production may have therapeutic implications.

Cited by 67 publications

References 17 publications

Nitric oxide-induced cellular stress and p53 activation in chronic inflammation

Nitric oxide-induced cellular stress and p53 activation in chronic inflammation

Identification of macrophage migration inhibitory factor and human neutrophil peptides 1–3 as potential biomarkers for gastric cancer

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

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