Expression of MHC Class II, CD70, CD80, CD86 and pro-inflammatory cytokines is differentially regulated in oral epithelial cells following bacterial challenge.
Oral epithelium may play a regulatory role in local immune responses when interacting with bacteria. The present study was undertaken to investigate the effects of selected bacterial pathogens found in periodontal and endodontic infections on oral epithelial cells. Expression of cell surface molecules (major histocompatibility complex (MHC) Class II, CD54, CD70, CD80 and CD86) and secretion of inflammatory cytokines (interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha) in response to selected bacterial challenge were examined on an immortalized oral epithelial cell line, HOK-18A and a skin epithelial cell line, HaCaT. Actinomyces viscosus, Actinomyces israelii, Fusobacterium nucleatum lipopolysaccharide (LPS) or primary human periradicular exudate from a granuloma were co-cultured with epithelial cells for 4 or 24 h. Subsequently, cell surface expression of MHC Class II, CD54, CD70, CD80 and CD86, along with pro-inflammatory cytokine levels were determined using flow cytometry, ELISA and RT-PCR. Results indicated that the selected oral bacteria have greater effects on oral versus skin epithelial cells. F. nucleatum increased MHC Class II and CD54 (ICAM-1) cell surface expression on HOK-18A and HaCaT cells. A. israelii also had enhancing effects on the expression of CD54 and MHC Class II. A. israelii and LPS induced a 2.8-fold (P < 0.001) and 4.4-fold (P < 0.005) TNF-alpha secretion, respectively, while F. nucleatum and LPS induced a 10-fold (P < 0.0004) and 6-fold (P < 0.01) IL-1beta secretion, respectively by HOK-18A. Interestingly, CD70, CD80, and CD86 were generally decreased upon bacteria and LPS challenge on HOK-18A. The effects of increased MHC Class II and decreased CD70 were also evident with challenge of human periradicular exudate on HOK-18A. The implications of the study are unique in that oral epithelial cells may play both activating and inhibitory roles in the host immune response towards infection by oral bacteria. We introduce a concept of 'dormancy' where the differential expression of key cell surface antigens on oral epithelial cells may keep the recruited immune effector cells in a state of unresponsiveness, thus contributing to the long term quiescent period observed in many periodontal and endodontic lesions.
Han
D C
DC
The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Medicine and Dentistry, Los Angeles, CA 90095, USA.
Huang
G T-J
GT
Lin
L M
LM
Warner
N A
NA
Gim
J S
JS
Jewett
A
A
D000190:Actinomyces / Q000276:immunology*; D000328:Adult; D015703:Antigens, CD / Q000032:analysis*; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen; D053282:CD27 Ligand; D002460:Cell Line; D016207:Cytokines / Q000032:analysis*; D004847:Epithelial Cells / Q000276:immunology; D005122:Exudates and Transudates; D005260:Female; D016967:Fusobacterium nucleatum / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000276:immunology; D008562:Membrane Glycoproteins / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D009061:Mouth Mucosa / Q000276:immunology*; D010484:Periapical Granuloma / Q000276:immunology; D012867:Skin / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D053282:CD27 Ligand; C505771:CD70 protein, human; C497964:CD86 protein, human; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1