bims-stacyt Biomed News
on Paracrine crosstalk between cancer and the organism
Issue of 2020‒06‒21
four papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge

  1. Gene X. 2020 Dec;5 100034
      Hyperglycemia activates innate leukocytes such as monocytes and induces pro-inflammatory cytokine expression, resulting in increased monocyte adhesion to aortic endothelial cells. In this study, we investigated whether high glucose and/or tumor necrosis factor (TNF) would enhance pro-inflammatory cytokine expression of tumor necrosis factor (TNF) and interleukin (IL)-1β (IL1B) by altering histone modifications in U937, a juvenile macrophage cell line. The mRNA levels of TNF and IL1B in U937 cells were significantly affected by glucose concentration and TNF treatment. Mono-methylated histone H3K4 signals around TNF and IL1B were lower in cells treated with high glucose compared with low glucose. Conversely, tri-methylated histone H3K4 and H3K36 signals were higher in cells treated with high glucose compared with low glucose. TNF treatment of U937 cells cultured in high glucose enhanced histone H3K36 tri-methylation, particularly around the gene regions of TNF and IL1B. Histone acetylation was induced by treatment with TNF in high-glucose medium. The induction of acetylation and tri-methylation of K4 and K36 of histone H3 around TNF and IL1B by treatment with high glucose and/or TNF was positively associated with the induction of these genes in juvenile macrophage U937 cells.
    Keywords:  CHD1, chromo-ATPase/helicase-DNA binding domain 1; ChIP, chromatin immunoprecipitation; FCS, fetal calf serum; H3K36 methylation; H3K4 methylation; Histone acetylation; IL, interleukin; Juvenile macrophage; P-TEFb, positive transcription elongation factor b; Pro-inflammatory cytokine; ROS, reactive oxygen species; TNF, tumor necrosis factor; U937
  2. Cytokine. 2020 Jun 11. pii: S1043-4666(20)30170-8. [Epub ahead of print]133 155154
      In obesity, macrophages infiltrate peripheral tissues and secrete pro-inflammatory cytokines that impact local insulin sensitivity. Lipopolysaccharide (LPS) and the saturated fatty acid (FA) palmitate polarise macrophages towards a pro-inflammatory phenotype in vitro and indirectly cause insulin resistance (IR) in myotubes. In contrast, unsaturated FAs confer an anti-inflammatory phenotype and counteract the actions of palmitate. To explore paracrine mechanisms of interest, J774 macrophages were exposed to palmitate ± palmitoleate or control medium and the conditioned media generated were screened using a cytokine array. Of the 62 cytokines examined, 8 were significantly differentially expressed following FA treatments. Notably, CXCL16 secretion was downregulated by palmitate. In follow-up experiments using ELISAs, this downregulation was confirmed and reversed by simultaneous addition of palmitoleate or oleate, while LPS also diminished CXCL16 secretion. To dissect potential effects of CXCL16, C2C12 myotubes were treated with palmitate to induce IR, recombinant soluble CXCL16 (sCXCL16), combined treatment, or control medium. Palmitate caused the expected reduction of insulin-stimulated Akt activation and glycogen synthesis, whereas simultaneous treatment with sCXCL16 attenuated these effects. These data indicate a putative role for CXCL16 in preservation of Akt activation and insulin signaling in the context of chronic low-grade inflammation in skeletal muscle.
    Keywords:  CXCL16; Insulin resistance; Macrophage; Muscle; Obesity
  3. Mol Cell. 2020 Jun 18. pii: S1097-2765(20)30355-5. [Epub ahead of print]78(6): 1019-1033
      The growing field of immune metabolism has revealed promising indications for metabolic targets to modulate anti-cancer immunity. Combination therapies involving metabolic inhibitors with immune checkpoint blockade (ICB), chemotherapy, radiation, and/or diet now offer new approaches for cancer therapy. However, it remains uncertain how to best utilize these strategies in the context of the complex tumor microenvironment (TME). Oncogene-driven changes in tumor cell metabolism can impact the TME to limit immune responses and present barriers to cancer therapy. These changes also reveal opportunities to reshape the TME by targeting metabolic pathways to favor immunity. Here we explore current strategies that shift immune cell metabolism to pro-inflammatory states in the TME and highlight a need to better replicate physiologic conditions to select targets, clarify mechanisms, and optimize metabolic inhibitors. Unifying our understanding of these pathways and interactions within the heterogenous TME will be instrumental to advance this promising field and enhance immunotherapy.
  4. Cytokine. 2020 Jun 16. pii: S1043-4666(20)30160-5. [Epub ahead of print]133 155144
      INTRODUCTION: Adipose tissue secretes various bioactive peptides/proteins, immune molecules and inflammatory mediators which are known as adipokines or adipocytokines. Adipokines play important roles in the maintenance of energy homeostasis, appetite, glucose and lipid metabolism, insulin sensitivity, angiogenesis, immunity and inflammation. Enormous number of studies from all over the world proved that adipocytokines are involved in the pathogenesis of diseases affecting nearly all body systems, which raises the question whether we can always blame adipocytokines as the triggering factor of every disease that may hit the body.OBJECTIVE: Our review targeted the role played by adipocytokines in the pathogenesis of different diseases affecting different body systems including diabetes mellitus, kidney diseases, gynecological diseases, rheumatologic disorders, cancers, Alzheimer's, depression, muscle disorders, liver diseases, cardiovascular and lung diseases.
    METHODOLOGY: We cited more than 33 recent literature reviews that discussed the role played by adipocytokines in the pathogenesis of different diseases affecting different body systems.
    CONCLUSION: More evidence is being discovered to date about the role played by adipocytokines in more diseases and extra research is needed to explore hidden roles played by adipokine imbalance on disease pathogenesis.
    Keywords:  Adipocytokines; Disease progression; Immunoinflammatory; Pathogenesis; Protective effect