Oesophageal defensin expression during Candida infection and reflux disease.
OBJECTIVE
Alpha (alpha-) and beta (beta-) defensins are major constituents of the innate defence system, providing rapid antimicrobial action. The expression of alpha- and beta-defensins in the oesophagus and stomach by quantitative, real-time, polymerase chain reaction (PCR) in healthy individuals was studied to define the influence of oesophageal Candida infection on their expression in comparison to oesophageal reflux disease.


METHODS
Biopsy samples were taken from the upper gastrointestinal tract, mRNA was extracted, reverse transcribed into cDNA and real-time reverse transcription PCR (RT-PCR) analysis measuring transcript number of a-defensins and ss-defensins performed. Standard curves allowed quantification of gene copies per weight of mRNA.


RESULTS
hBD-1, hBD-2 and hBD-3 had their highest expression levels in the oesophagus with factor 3 to 5 lower in the stomach. Candida oesophagitis resulted in massive up-regulation of hBD-2 (800-fold), while hBD-1 and hBD-3 expression were slightly increased. In addition, expression of HNP 1-3 was detected, indicating infiltration of neutrophil granulocytes. In reflux disease, an up-regulation of hBD-2 (20-fold) and hBD-3 (50-fold) could also be observed, while hBD-1, hBD-4 and HD5 remained unaffected. Cytokine expression of interleukin-1beta, interleukin-6 and interleukin-8 were increased in both groups, while interleukin-10 expression was elevated only in reflux lesions.


CONCLUSIONS
Candida colonization induced a high expression of antimicrobial peptides. In oesophageal reflux disease, induction of defensin expression could also be observed but to a lower degree. Therefore, up-regulation of defensins might protect against invasive candidiasis and keep the Candida infection limited to the mucosal surface.
Kiehne
Karlheinz
K
Department of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Germany. kkiehne@1med.uni-kiel.de
Brunke
Gabriele
G
Meyer
Daniela
D
Harder
Jürgen
J
Herzig
Karl-Heinz
KH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002177:Candidiasis / Q000276:immunology / Q000378:metabolism*; D004941:Esophagitis / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D004947:Esophagus / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000378:metabolism*; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D023084:alpha-Defensins / Q000096:biosynthesis*; D023083:beta-Defensins / Q000096:biosynthesis*
D007378:Interleukins; D012333:RNA, Messenger; D023084:alpha-Defensins; D023083:beta-Defensins