Increased beta 2 defensin in recurrent aphthous ulcer.
OBJECTIVE
It was hypothesized that beta 2 defensin (BD-2) is increased in RAU lesions compared with healthy controls to promote anti-microbial host defence.


METHODS
RAU and control mucosa samples were subjected to quantitative real-time PCR and immunostained for BD-2, CD68, mast cell tryptase and 4-hydroxynonenal (4HNE). The effect of tumour necrosis factor-α (TNF-α) ± interleukin-17C (IL-17C), without and with vitamin K3, was studied on BD-2 expression in epithelial SCC-25 cells.


RESULTS
Although BD-2 mRNA did not differ between healthy and RAU mucosa, BD-2 stained strongly in acute-phase RAU epithelium (P = 0.001). In controls, subepithelial BD-2(+) cells were mast cells and macrophages, whereas in RAU, most infiltrating leucocytes were BD-2(+) (P = 0.004). In cell culture, BD-2 was increased 124-fold by TNF-α (P < 0.0001) and 208-fold synergistically together with IL-17C (P < 0.0001). 4HNE staining of RAU epithelium was not significantly increased, and vitamin K3-induced reactive oxygen species (ROS) did not affect BD-2.


CONCLUSIONS
Anti-microbial BD-2 was not affected by oxidative stress but was highly increased in the epithelial and immigrant cells in the acute-phase RAU lesions, probably in part synergistically by TNF-α and epithelial IL-17C, which are known to be induced by activation of danger-signal receptors by pathogen- and/or damage-associated molecular patterns.
Department of Medicine, Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland; Department of Anatomy, Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
A
A
Al-Samadi
A
A
Salem
M
M
Ainola
J
J
Hietanen
R
R
Häyrinen-Immonen
Y T
YT
Konttinen
D000328:Adult; D000447:Aldehydes / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D013281:Stomatitis, Aphthous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D055815:Young Adult; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
D000447:Aldehydes; C106641:DEFB4A protein, human; D020381:Interleukin-17; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; C027576:4-hydroxy-2-nonenal
IL-17C; TNF-α; beta 2 defensin; oxidative stress; recurrent aphthous ulcer