Crucial Role of Macrophage Selenoproteins in Experimental Colitis

Kaushal, Naveen; Kudva, Avinash K.; Patterson, Andrew D.; Chiaro, Christopher; Kennett, Mary J.; Desai, Dhimant; Amin, Shantu; Carlson, Bradley A.; Cantorna, Margherita T.; Prabhu, K. Sandeep

doi:10.4049/jimmunol.1400347

Cited by 91 publications

(90 citation statements)

References 48 publications

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“…This could contribute to a decrease in DSS-induced inflammation due to selenium supplementation (data not shown). Recent studies from our laboratory have indicated that alternatively activated macrophages (M2) play an important role in protecting the colon from DSS-induced inflammation, under selenium supplemented conditions [27]. …”

Section: Resultsmentioning

confidence: 99%

Epigenetic regulation of inflammatory gene expression in macrophages by selenium

Narayan

Ravindra

Liao

et al. 2015

The Journal of Nutritional Biochemistry

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Acetylation of histone and non-histone proteins by histone acetyltransferases plays a pivotal role in the expression of pro-inflammatory genes. Given the importance of dietary selenium in mitigating inflammation, we hypothesized that selenium supplementation may regulate inflammatory gene expression at the epigenetic level. The effect of selenium towards histone acetylation was examined in both in vitro and in vivo models of inflammation by chromatin immunoprecipitation (ChIP) assays and immunoblotting. Our results indicated that selenium supplementation, as selenite, decreased acetylation of histone H4 at K12 and K16 in COX-2 and TNF promoters, and of the p65 subunit of the redox sensitive transcription factor NFκB in primary and immortalized macrophages. On the other hand, selenomethionine had a much weaker effect. Selenite treatment of HIV-1 infected human monocytes also significantly decreased the acetylation of H4 at K12 and K16 on the HIV-1 promoter, supporting the downregulation of proviral expression by selenium. A similar decrease in histone acetylation was also seen in the colonic extracts of mice treated with dextran sodium sulfate that correlated well with the levels of selenium in the diet. Bone marrow-derived macrophages from Trspfl/flCreLysM mice that lack expression of selenoproteins in macrophages confirmed the important role of selenoproteins in the inhibition of histone H4 acetylation. Our studies suggest that the ability of selenoproteins to skew the metabolism of arachidonic acid to contribute, in part, to their ability to inhibit histone acetylation. In summary, our studies suggest a new role for selenoproteins in the epigenetic modulation of pro-inflammatory genes.

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Section: Resultsmentioning

confidence: 99%

Epigenetic regulation of inflammatory gene expression in macrophages by selenium

Narayan

Ravindra

Liao

et al. 2015

The Journal of Nutritional Biochemistry

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“…Trsp knockout in myeloid lineages through a LysM-Cre driver led to increased oxidative stress, upregulated transcription of antioxidant enzymes, accumulation of reactive oxygen species, altered expression of extracellular matrix-related genes, and diminished migration through matrix [56, 59]. Furthermore, placing these mice on an acute DSS-induced colitis protocol resulted in worse colitis characterized by pronounced inflammation, neutrophil infiltration, edema, weight loss, shorter colon length, and expression of pro-inflammatory cytokines relative to WT mice treated with DSS [60]. While intestine epithelial-specific Trsp KO has not yet been described, these data suggest selenoprotein expression in myeloid-derived immune cells are potent suppressors of inflammation in the gut and likely contribute to inflammatory tumorigenesis.…”

Section: Investigating Selenoproteins Through Sec Trna Mutationsmentioning

confidence: 99%

Selenoproteins and oxidative stress-induced inflammatory tumorigenesis in the gut

Barrett

Short

Williams

2016

Cell. Mol. Life Sci.

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Selenium is an essential micronutrient that is incorporated into at least 25 selenoproteins encoded by the human genome, many of which serve antioxidant functions. Because patients with inflammatory bowel disease (IBD) demonstrate nutritional deficiencies and are at increased risk for colon cancer due to heightened inflammation and oxidative stress, selenoprotein dysfunction may contribute to disease progression. Over the years, numerous studies have analyzed the effects of selenoprotein loss and shown that they are important mediators of intestinal inflammation and carcinogenesis. In particular, recent work has focused on the role of selenoprotein P (SEPP1), a major selenium transport protein which also has endogenous antioxidant function. These experiments determined SEPP1 loss altered immune and epithelial cellular function in a murine model of colitis-associated carcinoma. Here, we discuss the current knowledge of SEPP1 and selenoprotein function in the setting of IBD, colitis, and inflammatory tumorigenesis.

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“…In addition, a combination of Se and vitamin E was found to exert a protective effect in rats by increasing their overall antioxidant capacity and total thiol levels in the colon [13]. Epidemiological studies have reported reduced Se concentrations in patients with CD or UC [14,15], and clinical studies have evidenced lower blood Se concentrations in IBD patients [5,16,17,18,19]. Se may have a beneficial effect in IBDs by modulating gut inflammation in combination with the gut microbiota [15].…”

Section: Introductionmentioning

confidence: 99%

“…Se may have a beneficial effect in IBDs by modulating gut inflammation in combination with the gut microbiota [15]. Thus, an increase in selenoproteins deactivates the prostaglandin E 2 (PGE 2 ) secreted by macrophages [14] by changing macrophage polarization from the macrophage-1 (M1) to the macrophage-2 (M2) phenotype, which in turn decreases gut inflammation [20]. These results suggest that higher Se concentrations than are currently recommended may be beneficial for IBD patients.…”

Section: Introductionmentioning

confidence: 99%

Ulcerative Colitis and Crohn’s Disease Are Associated with Decreased Serum Selenium Concentrations and Increased Cardiovascular Risk

et al. 2016

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The incidence of inflammatory bowel disease (IBD) and associated oxidative stress is increasing. The antioxidant mineral selenium (Se) was measured in serum samples from 106 IBD patients (53 with ulcerative colitis (UC) and 53 with Crohn’s disease (CD)) and from 30 healthy controls. Serum Se concentrations were significantly lower in UC and CD patients than in healthy controls (p < 0.001) and significantly lower in CD patients than in UC patients (p = 0.006). Se concentrations in patients were significantly influenced by sex, body mass index (BMI), the inflammatory biomarker α-1-antitrypsin, surgery, medical treatment, the severity, extent, and form of the disease and the length of time since onset (p < 0.05). Se concentrations in IBD patients were positively and linearly correlated with nutritional (protein, albumin, prealbumin, cholinesterase and total cholesterol) and iron status-related (hemoglobin, Fe and hematocrit) parameters (p < 0.05). A greater impairment of serum Se and cardiovascular status was observed in CD than in UC patients. An adequate nutritional Se status is important in IBD patients to minimize the cardiovascular risk associated with increased inflammation biomarkers, especially in undernourished CD patients, and is also related to an improved nutritional and body iron status.

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Crucial Role of Macrophage Selenoproteins in Experimental Colitis

Cited by 91 publications

References 48 publications

Epigenetic regulation of inflammatory gene expression in macrophages by selenium

Epigenetic regulation of inflammatory gene expression in macrophages by selenium

Selenoproteins and oxidative stress-induced inflammatory tumorigenesis in the gut

Ulcerative Colitis and Crohn’s Disease Are Associated with Decreased Serum Selenium Concentrations and Increased Cardiovascular Risk

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