Differential and coordinated expression of defensins and cytokines by gingival epithelial cells and dendritic cells in response to oral bacteria.
BACKGROUND
Epithelial cells and dendritic cells (DCs) both initiate and contribute to innate immune responses to bacteria. However, much less is known about the coordinated regulation of innate immune responses between GECs and immune cells, particularly DCs in the oral cavity. The present study was conducted to investigate whether their responses are coordinated and are bacteria-specific in the oral cavity.


RESULTS
The beta-defensin antimicrobial peptides hBD1, hBD2 and hBD3 were expressed by immature DCs as well as gingival epithelial cells (GECs). HBD1, hBD2 and hBD3 are upregulated in DCs while hBD2 and hBD3 are upregulated in GECs in response to bacterial stimulation. Responses of both cell types were bacteria-specific, as demonstrated by distinctive profiles of hBDs mRNA expression and secreted cytokines and chemokines in response to cell wall preparations of various bacteria of different pathogenicity: Fusobacterium nucleatum, Actinomyces naeslundii and Porphyromonas gingivalis. The regulation of expression of hBD2, IL-8, CXCL2/GRObeta and CCL-20/MIP3alpha by GECs was greatly enhanced by conditioned medium from bacterially activated DCs. This enhancement was primarily mediated via IL-1beta, since induction was largely attenuated by IL-1 receptor antagonist. In addition, the defensins influence DCs by eliciting differential cytokine and chemokine secretion. HBD2 significantly induced IL-6, while hBD3 induced MCP-1 to approximately the same extent as LPS, suggesting a unique role in immune responses.


CONCLUSIONS
The results suggest that cytokines, chemokines and beta-defensins are involved in interaction of these two cell types, and the responses are bacteria-specific. Differential and coordinated regulation between GECs and DCs may be important in regulation of innate immune homeostasis and response to pathogens in the oral cavity.
Yin
Lei
L
Department of Oral Biology, School of Dentistry, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, Box 357132, USA. leiyin@u.washington.edu
Chino
Takahiro
T
Horst
Orapin V
OV
Hacker
Beth M
BM
Clark
Edward A
EA
Dale
Beverly A
BA
Chung
Whasun O
WO
D001419:Bacteria / Q000187:drug effects / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000166:cytology* / Q000382:microbiology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D018448:Models, Immunological; D023083:beta-Defensins / Q000235:genetics* / Q000378:metabolism
D015415:Biomarkers; D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides; D023083:beta-Defensins