To investigate the influence of high salt on dextran sulfate sodium (DSS)-induced colitis in mice and explore the underlying mechanisms of this effect.

DSS and NaCl were used to establish the proinflammatory animal model. We evaluated the colitis severity. Flow cytometry was employed for detecting the frequencies of Th1, macrophages and Tregs in spleen, mesenteric lymph node and lamina propria. The important role of macrophages in the promotion of DSS-induced colitis by NaCl was evaluated by depleting macrophages with clodronate liposomes. Activated peritoneal macrophages and lamina propria mononuclear cells (LPMCs) were stimulated with NaCl, and proteins were detected by western blotting. Cytokines and inflammation genes were analyzed by enzyme-linked immunosorbent assay and RT-PCR, respectively.

The study findings indicate that NaCl up-regulates the frequencies of CD11b+ macrophages and CD4+IFN-γ+IL-17+ T cells in lamina propria in DSS-treated mice. CD3+CD4+CD25+Foxp3+ T cells, which can secrete high levels of IL-10 and TGF-β, increase through feedback in NaCl- and DSS-treated mice. Furthermore, clodronate liposomes pretreatment significantly alleviated DSS-induced colitis, indicating that macrophages play a vital role in NaCl proinflammatory activity. NaCl aggravates peritoneal macrophage inflammation by promoting the expressions of interleukin (IL)-1, IL-6 and mouse inducible nitric oxide synthase. Specifically, high NaCl concentrations promote p38 phosphorylation in lipopolysaccharide- and IFN-γ-activated LPMCs mediated by SGK1.

Proinflammatory macrophages may play an essential role in the onset and development of NaCl-promoted inflammation in DSS-induced colitis. The underlining mechanism involves up-regulation of the p38/MAPK axis.

Considering epidemiological, genetic and immunological data, we can conclude that the inflammatory bowel diseases are heterogeneous disorders of multifactorial etiology in which hereditability and environment interact to produce the disease. It is probable that patients have a genetic predisposition for the development of the disease coupled with disturbances in immunoregulation. Several genes have been so far related to the diagnosis of Crohn's disease. Those genes are related to innate pattern recognition receptors, to epithelial barrier homeostasis and maintenance of epithelial barrier integrity, to autophagy and to lymphocyte differentiation. So far, the most strong and replicated associations with Crohn's disease have been done with NOD2, IL23R and ATG16L1 genes. Many genes have so far been implicated in prognosis of Crohn's disease and many attempts have been made to classify genetic profiles in Crohn's disease. CARD15 seems not only a susceptibility gene, but also a disease-modifier gene for Crohn's disease. Enriching our understanding on Crohn's disease genetics is important but when combining genetic data with functional data the outcome could be of major importance to clinicians.

Considering the epidemiological, genetic and immunological data, we can conclude that the inflammatory bowel diseases are heterogeneous disorders of multifactorial etiology in which hereditability and environment interact to produce the disease. It is probable that patients have a genetic predisposition for the development of the disease coupled with disturbances in immunoregulation. Several genes have so far been related to the diagnosis of Crohn's disease. These genes are related to innate pattern recognition receptors, to epithelial barrier homeostasis and maintenance of epithelial barrier integrity, to autophagy and to lymphocyte differentiation. So far, the strongest and most replicated associations with Crohn's disease have been demonstrated with NOD2, IL23R and ATG16L1 genes. Many genes have so far been implicated in the prognosis of Crohn's disease and many attempts have been made for classification of genetic profiles in Crohn's disease. CARD15 seems to be not only a susceptibility gene, but also a disease-modifier gene for Crohn's disease. Enriching our understanding of Crohn's disease genetics is of value, but when combining genetic data with functional data the outcome could be of major importance to clinicians.