Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The increased incidence of systemic lupus erythematosus (SLE) in recent decades might be related to changes in modern dietary habits. Since sodium chloride (NaCl) promotes pathogenic T cell responses, we hypothesize that excessive salt intake contributes to the increased incidence of autoimmune diseases, including SLE. Given the importance of dendritic cells (DCs) in the pathogenesis of SLE, we explored the influence of an excessive sodium chloride diet on DCs in a murine SLE model. We used an induced lupus model in which bone marrow-derived dendritic cells (BMDCs) were incubated with activated lymphocyte-derived DNA (ALD-DNA) and transferred into C57BL/6 recipient mice. We observed that a high-salt diet (HSD) markedly exacerbated lupus progression, which was accompanied by increased DC activation. NaCl treatment also stimulated the maturation, activation and antigen-presenting ability of DCs in vitro. Pretreatment of BMDCs with NaCl also exacerbated BMDC-ALD-DNA-induced lupus. These mice had increased production of autoantibodies and proinflammatory cytokines, more pronounced splenomegaly and lymphadenopathy, and enhanced pathological renal lesions. The p38 MAPK-STAT1 pathway played an important role in NaCl-induced DC immune activities. Taken together, our results demonstrate that HSD intake promotes immune activation of DCs through the p38 MAPK-STAT1 signaling pathway and exacerbates the features of SLE. Thus, changes in diet may provide a novel strategy for the prevention or amelioration of lupus or other autoimmune diseases.
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PMID:High salt diet accelerates the progression of murine lupus through dendritic cells via the p38 MAPK and STAT1 signaling pathways. 3229 43

Consumption of a Western-type diet has been linked to gut-microbiota-mediated colon inflammation that constitutes a risk factor for colorectal cancer. A high salt diet (HSD) exacerbates IL-17A-induced inflammation in inflammatory bowel disease and other autoimmune diseases. Enterotoxigenic Bacteroides fragilis (ETBF) is a gut commensal bacterium and reported to be a potent initiator of colitis via secretion of the Bacteroides fragilis toxin (BFT). BFT induces ectodomain cleavage of E-cadherin in colonic epithelial cells, consequently leading to cell rounding, epithelial barrier disruption, and the secretion of IL-8, which promotes tumorigenesis in mice via IL-17A-mediated inflammation. A HSD is characteristic of the Western-type diet and can exhibit inflammatory effects. However, a HSD induces effects in ETBF-induced colitis and tumorigenesis remain unknown. In this study, we investigated HSD effects in ETBF-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis as well as ETBF colitis mice. Unexpectedly, ETBF-infected mice fed a HSD exhibited decreased weight loss and splenomegaly and reduction of colon inflammation. The HSD significantly decreased the expression of IL-17A and inducible nitric oxide synthase (iNOS) in the colonic tissues of ETBF-infected mice. In addition, serum levels of IL-17A and nitric oxide (NO) were also diminished. However, HT29/C1 colonic epithelial cells treated with sodium chloride showed no changes in BFT-induced cellular rounding and IL-8 expression. Furthermore, HSD did not affect ETBF colonization in mice. In conclusion, HSD decreased ETBF-induced tumorigenesis through suppression of IL-17A and iNOS expression in the colon. HSD also inhibited colonic polyp numbers in the ETBF-infected AOM/DSS mice. Taken together, these findings suggest that a HSD consumption inhibited ETBF-promoted colon carcinogenesis in mice, indicating that a HSD could have beneficial effects under certain conditions.
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PMID:Dietary Salt Administration Decreases Enterotoxigenic Bacteroides fragilis (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation. 3312 15