bims-stacyt Biomed news on
Starvation pathways leading to cytokine regulation
Issue of 2017‒12‒31
three papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge


  1. Arch Oral Biol. 2017 Dec 16. doi: 10.1016/j.archoralbio.2017.12.01187
    Abstract:  OBJECTIVE: To observe if inhibition of the receptor for advanced glycation endproducts (RAGE) promotes proliferation and repair of human periodontal ligament fibroblasts (hPDLFs) stimulated by high glucose. In addition, we also discuss the effects of the NF-κB signaling pathway in relation to this process. METHODS: Primary cultured hPDLFs were exposed to either low glucose (5.5 mmol/L) or high glucose (25 mmol/L), and RAGE expression was measured by Western blot analysis. Cells were cultured in high glucose with different concentrations of the RAGE inhibitor, FPS-ZM1. We measured cell proliferation using the Cell Counting Kit-8 and expression of collagen type 1 and fibronectin by real-time PCR and ELISA, respectively. The relative protein expression levels of NF-κB p65 and phosphorylated p65 were measured by Western blot analysis. RESULTS: High glucose enhanced RAGE expression and suppressed cell growth. While FPS-ZM1 increased proliferation and expression of repair-related factors in high glucose, there was a concurrent decline in the phosphorylation level of NF-κB p65. CONCLUSION: FPS-ZM1 rescued the proliferative capacity and repair capability of hPDLFs via the RAGE-NF-κB signaling pathway in response to high glucose.
    Keywords:  Human periodontal ligament fibroblasts; Inhibitor; NF-κB signaling pathway; Proliferation and repair; Receptor for advanced glycation endproducts
  2. Adv Exp Med Biol. 2017 ;doi: 10.1007/978-3-319-67577-0_101036
    Abstract:  Rodent and clinical studies have documented that myeloid cell infiltration of tumors is associated with neutrophilia, lymphocytopenia and poor patient outcomes. This contrasts with lymphocyte infiltration of tumors, which is associated with improved outcomes. Lifestyle parameters such as high fat diet s and omega (ω)-6 polyunsaturated fatty acids (PUFA) intake may influence these inflammatory parameters including extramedullary myelopoiesis that can contribute to a metastatic "niche". While, tumor secretion of growth factors (GFs) and chemokines regulate tumor-immune-cell crosstalk, in this chapter, we also emphasize how lifestyle choices, including, obesity, high-fat and high ω-6 PUFA dietary content, contribute to inflammation and myeloid cell infiltration of tumors. A relationship between obesity and high-fat diets (notably the saturated fats in Western diets) and tumor incidence, metastasis, and poor outcomes is generally accepted. However, the mechanisms of dietary promotion of inflammatory microenvironments and targeted drugs to inhibit the clinical sequel remain an unmet challenge. One approach, modification of dietary intake may have a preventative or therapeutic approach to regulate tumor-associated inflammation and remains an attractive, but little studied intervention.
    Keywords:  High fat diet; Immune escape; Infiltration; Invasion; MDSC; Metastasis; PUFA; Seed and soil; TAM; Vasculogenesis
  3. Adv Exp Med Biol. 2017 ;doi: 10.1007/978-3-319-67577-0_31036
    Abstract:  The tumor microenvironment consists of a complex milieu of cells and factors that maintain equilibrium between tumor progression and destruction. Characterization of the immune contexture in primary tumors has consistently shown that T lymphocytes are an integral predictor of improved clinical outcome. This is notably true in colorectal carcinoma where high densities of cytotoxic or memory T lymphocytes in the invasive margin and the center of the primary tumor predict better patient survival, a measure termed Immunoscore. Since a high Immunoscore and pre-existing adaptive immune response are significantly correlated with improved clinical outcome, it is essential to understand the mechanisms underlying functional T lymphocyte infiltration into the tumor. The ability of cytolytic and memory T lymphocytes to migrate into tumors is regulated by multiple strategies including T lymphocyte help, homing factors, cytokines, tumor genotype, angiogenesis, lymphangiogenesis, and neurological signals. This chapter will discuss the predominant factors that mediate T-lymphocyte infiltration into tumors and how analysis of these biomarkers determine patients' disease-related survival and predicts response to cancer therapy.
    Keywords:  Biomarkers; Chemokines; Colorectal cancer; Immunology; Immunoscore; Immunotherapy; Memory T lymphocytes; T-lymphocyte trafficking; Tumor microenvironment