Inducible expression of human beta-defensin 2 by Fusobacterium nucleatum in oral epithelial cells: Multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier
S. Krisanaprakornkit et al., Inducible expression of human beta-defensin 2 by Fusobacterium nucleatum in oral epithelial cells: Multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier, INFEC IMMUN, 68(5), 2000, pp. 2907-2915
Human gingival epithelial cells (HGE) express two antimicrobial peptides of
the beta-defensin family, human beta-defensin 1 (hBD-1) and hBD-2, as well
as cytokines and chemokines that contribute to innate immunity, In the pre
sent study, the expression and transcriptional regulation of hBD-2 was exam
ined. HBD-2 mRNA was induced by cell wall extract of Fusobacterium nucleatu
m, an oral commensal microorganism, but not by that of Porphyromonas gingiv
alis, a periodontal pathogen, HBD-2 mRNA was also induced by the proinflamm
atory cytokine tumor necrosis factor alpha (TNF-alpha) and phorbol myristat
e acetate (PMA), an epithelial cell activator, HBD-2 mRNA was also expresse
d in 14 of 15 noninflamed gingival tissue samples. HBD-2 peptide was detect
ed by immunofluorescence in HGE stimulated with F. nucleatum cell wall, con
sistent with induction of the mRNA by this stimulant. Kinetic analysis indi
cates involvement of multiple distinct signaling pathways in the regulation
of hBD-2 mRNA; TNF-alpha and F. nucleatum cell wall induced hBD-2 mRNA rap
idly (2 to 4 h), while PMA stimulation was slower (similar to 10 h). In con
trast, each stimulant induced interleukin 8 (IL-8) within 1 h, The role of
TNF-alpha as an intermediary in F. nucleatum signaling was ruled out by add
ition of anti TNF-alpha that did not inhibit hBD-2 induction, However, inhi
bitor studies show that F. nucleatum stimulation of hBD-2 mRNA requires bot
h new gene transcription and new protein synthesis, Bacterial lipopolysacch
arides isolated from Escherichia coli and F, nucleatum were poor stimulants
of hBD-2, although they up-regulated IL-8 mRNA. Collectively, our findings
show inducible expression of hBD-2 mRNA via multiple pathways in HGE in a
pattern that is distinct from that of IL-8 expression. We suggest that diff
erent aspects of innate immune responses are differentially regulated and t
hat commensal organisms have a role in stimulating mucosal epithelial cells
in maintaining the barrier that contributes to homeostasis and host defens
e.