title: Areca nut extracts enhance the development of CD11b(+) Gr-1(+)  cells with the characteristics of myeloid-derived suppressor cells in antigen-stimulated mice.
abstract: BACKGROUND
  Areca quid chewing is an etiological factor contributing to the development of oral cancer and pre-cancers, whose pathophysiology has been linked to inflammation and immune deterioration. Myeloid-derived suppressor cells (MDSC) play a key role in the regulation of immunity under certain pathological conditions, such as inflammation and cancer. As areca nut extracts (ANE) have been reported to induce a proinflammatory effect in antigen-stimulated mice, we hypothesized that ANE might enhance the development of MDSC.
  
  
  METHODS
  Ovalbumin (OVA)-sensitized BALB/c mice were daily administered with ANE (5-50 mg/kg), polyphenol-enriched ANE (PANE; 25 mg/kg) or arecoline (5 mg/kg) by intraperitoneal injection for 10 doses. The mouse footpads were then subcutaneously challenged with OVA to induce local inflammatory responses.
  
  
  RESULTS
  ANE and PANE treatment significantly increased the spleen index and the population of CD11b(+) Gr-1(+) cells in the spleen and peripheral blood, whereas arecoline was inactive. In addition, ANE and PANE treatment enhanced the expression of cytokines and enzymes associated with the immunosuppressive function of MDSC, including IL-10, arginase-I and iNOS in splenic CD11b(+) cells. Concordantly, ANE and PANE treatment augmented the infiltration of Gr-1(+) IL-10(+) cells in the footpads challenged with OVA.
  
  
  CONCLUSIONS
  Our results suggested that areca nut constituents, in particular, polyphenols enhanced the development of myeloid-derived suppressor cells in vivo, which may be a critical mechanism linking inflammation and the compromised immunity reported to be associated with the pathophysiology of areca-related oral diseases.
authors.affiliation: Animal Cancer Center, Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Wang
authors.forename: Hung-Li
authors.initials: HL
authors.lastname: Lin
authors.forename: Hong-Jen
authors.initials: HJ
authors.lastname: Liang
authors.forename: Tong-Rong
authors.initials: TR
authors.lastname: Jan
mesh_terms: D000818:Animals; D001114:Areca; D001115:Arecoline / Q000494:pharmacology; D001119:Arginase / Q000032:analysis; D001835:Body Weight; D039481:CD11b Antigen / Q000187:drug effects* / Q000276:immunology; D018929:Cell Culture Techniques; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D018679:Cholinergic Agonists / Q000494:pharmacology; D007108:Immune Tolerance / Q000276:immunology*; D007114:Immunization; D018836:Inflammation Mediators / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D009754:Nuts; D009929:Organ Size; D010047:Ovalbumin / Q000276:immunology; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology; D019707:Receptors, Chemokine / Q000187:drug effects* / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000473:pathology
chemical_list: D039481:CD11b Antigen; D018679:Cholinergic Agonists; C503133:Gr-1 protein, mouse; D018836:Inflammation Mediators; D010936:Plant Extracts; D059808:Polyphenols; D019707:Receptors, Chemokine; D016753:Interleukin-10; D001115:Arecoline; D010047:Ovalbumin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C544448:Arg1 protein, mouse; D001119:Arginase