Areca Nut Extract Induced Inflammatory Reactions and Enhanced the Development of Myeloid-derived Suppressor Cells in Ovalbumin-sensitized Mice
Date Issued
2010
Date
2010
Author(s)
Lin, Hung-Li
Abstract
Areca nut chewing is an etiological factor for oral cancer and pre-cancer lesions. Clinical studies suggest that prolonged tissue inflammation and immune deterioration are closely associated with the pathophysiology of areca-related oral diseases. Although recent in vitro studies demonstrated that areca nut extract (ANE) influenced the functionality of lymphocytes and neutrophils, the in vivo immunomodulatory effect of areca nut ingredients remains mostly unclear. The present studies investigated the effect of ANE on antigen-specific immune responses in ovalbumin (OVA)-sensitized mice. BALB/c mice were daily administered with ANE by intraperitoneal (IP; 5-50 mg/kg) injection or oral gavage (50-200 mg/kg) from day 1-5 and 8-12. The mice were IP sensitized with ovalbumin (OVA) absorbed to alum on day 3 and their footpads were subcutaneously challenged with OVA (10 microgram in 20 microliter saline) on day 13 to induce delayed-type hypersensitivity (DTH) reactions. IP administration of ANE dose-dependently increased the spleen index and the number of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSC) in the spleen. Morphologic examination revealed that the CD11b+ cells included granulocytic and monocytic cells. Lipopolysaccharide (LPS)-induced IL-10 production by CD11b+ cells of IP ANE-treated mice was significantly increased. The phagocytic activity and TNF-alpha expression by the splenic CD11b+ cells were elevated in ANE-treated groups. IP ANE also enhanced OVA-specific IFN-gamma production and LPS-induced iNOS mRNA expression by splenocytes. The serum levels of OVA-specific IgM and IgG1 was significantly attenuated in mice treated with IP ANE (5 and 25 mg/kg), whereas OVA-specific IgG2a were enhanced in mice treated with the high dose of ANE (50 mg/kg). In addition, an increase in OVA challenge-induced footpad swelling, and a greater infiltration of inflammatory cells, including CD3+ and F4/80+ cells was observed in ANE-treated mice. The number of IFN-gamma secreting cells in the footpads was also increased. Taken together, these results demonstrated that IP administration of ANE enhanced the production of antigen-specific IFN-gamma, produced a pro-inflammatory effect, and induced the development of CD11b+Gr-1+ MDSC. The inflammation may induce the accumulation of CD11b+Gr-1+ MDSC which have the ability to secret IL-10. Further studies were needed to clarify the suppressive nature of the MDSC.
Subjects
areca nut extract
myeloid-derived suppressor cell
IFN-gamma
inflammation
SDGs
Type
thesis
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