Gene expression of tumor necrosis factor receptor associated‐factor (<scp>TRAF</scp>)‐1 and <scp>TRAF</scp>‐2 in inflammatory bowel disease

Qiao, Yu; Shen, Jun; Gu, Yu; Jin, Tengchuan; Xu, Xi; Huang, Mingliang; Ran, Zhi Hua

doi:10.1111/1751-2980.12044

Cited by 32 publications

(30 citation statements)

References 28 publications

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“…Furthermore, in human inflammatory bowel disease (IBD) specimens, the mRNA level of EZH2 was negatively correlated with that of TRAF2 or TRAF5, suggesting that the decreased EZH2 expression in IBD patients causes augmented TNF-a-induced NF-kB signaling mediated by TRAF2 and TRAF5. In support of this, the expression of TRAF2 and TRAF5 was upregulated in the inflamed colonic tissues of IBD patients (38,39). In addition, the overexpression of TRAF2 or TRAF5 might be involved in colon cancer development (40,41).…”

Section: Discussionmentioning

confidence: 65%

TRAF5 Deficiency Ameliorates the Severity of Dextran Sulfate Sodium Colitis by Decreasing TRAF2 Expression in Nonhematopoietic Cells

et al. 2020

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TNFR-associated factor 5 (TRAF5) is a cytosolic adaptor protein and functions as an inflammatory regulator. However, the in vivo function of TRAF5 remains unclear, and how TRAF5 controls inflammatory responses in the intestine is not well understood. In this study, we found that intestinal epithelial cells from Traf5 2/2 mice expressed a significantly lower level of NF-kB-regulated proinflammatory genes, such as Tnf, Il6, and Cxcl1, as early as day 3 after dextran sulfate sodium (DSS) exposure when compared with wild-type mice. The intestinal barrier integrity of DSS-treated Traf5 2/2 mice remained intact at this early time point, and Traf5 2/2 mice showed decreased body weight loss and longer colon length at later time points. Surprisingly, the protein level of TRAF2, but not TRAF3, was reduced in colon tissues of Traf5 2/2 mice after DSS, indicating the requirement of TRAF5 for TRAF2 protein stability in the inflamed colon. Experiments with bone marrow chimeras confirmed that TRAF5 deficiency in nonhematopoietic cells caused the attenuated colitis. Our in vitro experiments demonstrated that proinflammatory cytokines significantly promoted the degradation of TRAF2 protein in Traf5 2/2 nonhematopoietic cells in a proteasome-dependent manner. Collectively, our data suggest a novel regulatory function of TRAF5 in supporting the proinflammatory function of TRAF2 in nonhematopoietic cells, which may be important for acute inflammatory responses in the intestine.

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Section: Discussionmentioning

confidence: 65%

TRAF5 Deficiency Ameliorates the Severity of Dextran Sulfate Sodium Colitis by Decreasing TRAF2 Expression in Nonhematopoietic Cells

et al. 2020

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“…Immune-related genes complement component 5 (C5)/TRAF1 located on Chromosome 9q33-34 is identified as a risk factor for rheumatoid arthritis [11], uveitis in juvenile idiopathic arthritis [12], multiple autoimmune diseases such as SLE [13]. TRAF1 is associated with susceptibility to autoimmune thyroid disease [14], IBD [15] and DMBA/solar UVR-induced skin carcinogenesis [16]. However, the role of TRAF1 in infectious diseases such as C. albicans infection remains unknown.…”

Section: Introductionmentioning

confidence: 99%

TRAF1 suppresses antifungal immunity through CXCL1-mediated neutrophil recruitment during Candida albicans intradermal infection

et al. 2020

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Background: Candida albicans is the most common opportunistic human fungal pathogen. The chemokine ligand CXCL1 plays a protective role in fungal infection through the recruitment of neutrophils. TRAF1 (tumor necrosis factor-associated factor 1) can be highly induced by proinflammatory stimuli such as LPS and TNF and has been implicated in septic shock. However, the role of TRAF1 in infection, especially fungal infection, remains elusive. Herein, we reveal that TRAF1 suppresses the antifungal immune response to Candida albicans intradermal infection through the regulation of CXCL1 induction and neutrophil recruitment. Methods: A mouse model of C. albicans intradermal infection was established. The Traf1 −/− mice and Traf1 −/− immortalized human keratinocytes were generated. The p65 inhibitor triptolide, STAT1 inhibitor fludarabine, neutrophil-depletion antibody Ly6G, and neutralizing antibody for CXCL1 were utilized. The expression of proinflammatory cytokines and chemokines was assessed by real-time PCR and ELISA, and the activation of signaling molecules was analyzed by Western blotting. Hematoxylin and eosin staining and periodic acid Schiff staining were used for histology or fungal detection, respectively. The immunofluorescence and flow cytometry analyses were employed in the assessment of immune cell infiltration. Bone marrow transplantation and adoptive transfer experiments were conducted to establish a role for TRAF1 in the macrophage compartment in fungal skin infection. Results: TRAF1-deficient mice demonstrated improved control of Candida albicans intradermal infection, and concomitant increase in neutrophil recruitment and reduction in fungal burden. The chemokine CXCL1 was upregulated in the TRAF1-deficient macrophages treated with heat-killed C. albicans. Mechanistically, TRAF1deficient macrophages showed increased activation of transcription factor NFκB p65. The human CXCL8 was also highly induced in the TRAF1-deficient human keratinocytes upon TNF stimulation through decreasing the activation of transcription factor STAT1. TRAF1-deficient macrophages played a critical role in containing the C. albicans skin infection in vivo. Conclusion: TRAF1-deficient mice can better control fungal infection in the skin, a process attributable to the CXCL-neutrophil axis. Mechanistically, TRAF1 likely regulates CXCL1 expression in both macrophages and keratinocytes through the transcriptional factor NFκB and STAT1, respectively. Our finding offers new insight into the understanding of the immune regulatory mechanisms in host defense against C. albicans infection.

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“…Furthermore, a recent study performed on IBD patients showed enhanced expression levels of TRAF-1 and -2 in the colonic mucosal of IBD patients compared to healthy controls. Moreover, inflamed tissues had higher TRAF-1 and -2 expression than non-inflamed tissues, suggesting that their altered expression level might be an early event in the disease pathogenesis [97]. We demonstrated enhanced TRAF-2 expression in the colon of DSS treated mice, and E121 treatment reduced its expression back to control level (Fig 5).…”

Section: Discussionmentioning

confidence: 65%

Anti-Inflammatory Properties of the Enaminone E121 in the Dextran Sulfate Sodium (DSS) Colitis Model

2016

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BackgroundEnaminones are synthetic compounds with an established role in the prevention of various forms of seizures. Recent evidence suggests potent anti-tussive, bronchodilation and anti-inflammatory properties. Pre-treatment with particularly E121 compound resulted in a decrease in leukocyte recruitment in the ovalbumin induced-model of asthma, immune cell proliferation and cytokine release in vitro. We hypothesize that E121 might serve as a therapeutic potential in intestinal inflammation through modulating immune cell functions.MethodsColitis was induced by daily dextran sulfate sodium (DSS) administration for 5 days, and its severity was determined by gross and histological assessments. The plasma level of various cytokines was measured using flow cytometry-based assay. The colonic expression/ phosphorylation level of various molecules was determined by immunofluorescence and western blotting. The effects of E121 treatment on in vitro neutrophil chemotaxis (under-agarose assay), superoxide release (luminol oxidation assay) and apoptosis (annexin V/7AAD) were also determined.ResultsDSS-induced colitis in mice was significantly reduced by daily E121 treatment (30–100 mg/kg) at gross and histological levels. This effect was due to modulated plasma levels of interleukin (IL-2) and colonic expression levels of various signaling molecules and proteins involved in apoptosis. In vitro neutrophil survival, chemotaxis, and superoxide release were also reduced by E121 treatment.ConclusionOur results indicate important anti-inflammatory actions of E121 in the pathogenesis of IBD.

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Gene expression of tumor necrosis factor receptor associated‐factor (TRAF)‐1 and TRAF‐2 in inflammatory bowel disease

Abstract: The activation of TRAF-1 and TRAF-2 may be early events in the pathogenesis of IBD and their functions are not quite the same.

Cited by 32 publications

References 28 publications

TRAF5 Deficiency Ameliorates the Severity of Dextran Sulfate Sodium Colitis by Decreasing TRAF2 Expression in Nonhematopoietic Cells

TRAF5 Deficiency Ameliorates the Severity of Dextran Sulfate Sodium Colitis by Decreasing TRAF2 Expression in Nonhematopoietic Cells

TRAF1 suppresses antifungal immunity through CXCL1-mediated neutrophil recruitment during Candida albicans intradermal infection

Anti-Inflammatory Properties of the Enaminone E121 in the Dextran Sulfate Sodium (DSS) Colitis Model

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