Areca nut extracts enhance the development of CD11b(+) Gr-1(+) cells with the characteristics of myeloid-derived suppressor cells in antigen-stimulated mice.

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. 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. 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. 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.

Wang CC ，Lin HL ，Liang HJ ，Jan TR ... -  《-》

Areca-nut extract modulates antigen-specific immunity and augments inflammation in ovalbumin-sensitized mice.

Wang CC ，Lin HL ，Wey SP ，Jan TR ... -  《-》

Myeloid-derived suppressor cell activation by combined LPS and IFN-gamma treatment impairs DC development.

Greifenberg V ，Ribechini E ，Rössner S ，Lutz MB ... -  《-》

Areca nut extract suppresses T-cell activation and interferon-gamma production via the induction of oxidative stress.

Wang CC ，Liu TY ，Wey SP ，Wang FI ，Jan TR ... -  《FOOD AND CHEMICAL TOXICOLOGY》

Hierarchy of immunosuppressive strength among myeloid-derived suppressor cell subsets is determined by GM-CSF.

Dolcetti L ，Peranzoni E ，Ugel S ，Marigo I ，Fernandez Gomez A ，Mesa C ，Geilich M ，Winkels G ，Traggiai E ，Casati A ，Grassi F ，Bronte V ... -  《-》