Alpha-defensin increase in peripheral blood mononuclear cells from patients with hepatitis C virus chronic infection.
The alpha-defensin genes promoter regions contain a putative nuclear factors of activated T cells (NFAT)-binding site and it is known that hepatitis C virus (HCV) core protein activates the interleukin (IL)-2 gene transcription through the NFAT pathway. The aims of this study were to investigate if HCV affects the alpha-defensin expression in peripheral human mononuclear cells (PBMCs) and to evaluate the existence of a correlation between alpha-defensins and liver damage in patients with chronic hepatitis C. Ninety patients with chronic hepatitis C, 30 with chronic hepatitis B and 25 healthy controls were enrolled. Alpha-defensins were identified and quantified in PBMCs by mass spectrometry, enzyme-linked immunosorbent assay, antibacterial activity and mRNA levels. PBMCs from three patients and controls were stimulated with HCV core protein, hepatitis B virus core antigen and the alpha-defensin mRNAs level was quantified. We found that HCV core protein activates in vitro the alpha-defensin transcription. Alpha-defensin levels in patients with chronic hepatitis C (mean +/- SD = 1.103 +/- 0.765 ng/10(6) cells), chronic hepatitis B (0.53 +/- 0.15) and healthy controls (0.217 +/- 0.09) resulted significantly different (P < 0.001). In patients with chronic hepatitis C, the alpha-defensin levels and antibacterial activity correlate with the liver fibrosis. Our data suggest that HCV induces alpha-defensin expression. The high linear correlation of alpha-defensin levels with advancing fibrosis makes the measure of these peptides a reliable marker to evaluate fibrosis stage.
Aceti
A
A
Dipartimento di Malattie Infettive, II Factoltà di Medicina e Chiurgia, Università di Roma La Sapienza, Azienda Ospedaliera Sant'Andrea, Roma, Italy. antonio.aceti@uniromal.it
Mangoni
M L
ML
Pasquazzi
C
C
Fiocco
D
D
Marangi
M
M
Miele
R
R
Zechini
B
B
Borro
M
M
Versace
I
I
Simmaco
M
M
D000328:Adult; D000890:Anti-Infective Agents / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008103:Liver Cirrhosis / Q000097:blood / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D023084:alpha-Defensins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics / Q000276:immunology
D000890:Anti-Infective Agents; D012333:RNA, Messenger; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C406427:human neutrophil peptide 3