title: Higher concentrations of interferon-gamma enhances uptake and transport of dietary antigens by human intestinal cells: a study using cultured Caco-2 cells.
abstract: Besides functioning as a mucosal barrier and transporting nutrients, intestinal epithelial cells (IECs) also serve as antigen-presenting cells (APCs). Modification of protein antigens by proteolysis is one of the principal steps in antigen presentation to Th cells. We used a Caco-2 intestinal epithelial cell line to investigate the transepithelial transport of the dietary antigen, ovalbumin (OVA). We also examined the effects of the proinflammatory cytokine interferon-gamma (IFN-gamma) on the antigen transport process in Caco-2 cell layers. Caco-2 cell layers transferred both intact and degraded OVA from the mucosal to the serosal side. IFN-gamma stimulated OVA transport and most of the transported OVA in such cells were degraded. We also examined OVA uptake by Caco-2 cells using immunohistochemical means. Caco-2 cells incorporated OVA in a time-dependent manner and IFN-gamma significantly enhanced antigen internalization. Flow cytometry also demonstrated that IFN-gamma elevated the internalization of FITC-OVA. We also determined the effects of low and high concentrations of IFN-gamma on mucosal permeability and internalization of FITC-OVA. Although both 10 and 50 ng/mL IFN-gamma stimulated mucosal permeability to the same extent, more FITC-OVA was internalized by Caco-2 cells incubated with 50 than with 10 ng/mL IFN-gamma. These results suggest that the effects of IFN-gamma on mucosal permeability and the internalization of antigens by intestinal epithelial cells are brought about by different mechanisms. Therefore, higher concentrations of IFN-gamma stimulate the uptake, processing, and transport of dietary antigens by IECs.
authors.affiliation: Department of Nutrition, Faculty of Human Life Sciences, Yamaguchi Prefectural University, 3-2-1 Sakurabatake, Yamaguchi 753-8502, Japan. koda@yamaguchi-pu.ac.jp
authors.forename: Tomoko
authors.initials: T
authors.lastname: Koda
authors.forename: Hisanori
authors.initials: H
authors.lastname: Minami
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ogawa
authors.forename: Mariko
authors.initials: M
authors.lastname: Yamano
authors.forename: Eiji
authors.initials: E
authors.lastname: Takeda
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D004847:Epithelial Cells; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D010047:Ovalbumin / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects
chemical_list: D007371:Interferon-gamma; D010047:Ovalbumin