Interleukin-8 concentration in peritoneal fluid of patients with endometriosis and modulation of interleukin-8 expression in human mesothelial cells.
Interleukin-8 (IL-8) is a chemoattractant and activating factor for human neutrophlls and a potent angiogenic agent. The peritoneal fluid of women with endometriosis has been shown to have increased neutrophil chemotactic activity. We postulate that IL-8 may be an important modulator in the pathogenesis of endometriosis and adhesion formation. We first investigated IL-8 concentrations in the peritoneal fluid of women with or without endometriosis, then assessed peritoneal mesothelial cells as a potential source of peritoneal fluid IL-8. Northern blot analysis and enzyme-linked immunosorbent assay (ELISA) were used to investigate IL-8 mRNA and protein modulation. The mean concentration of IL-8 in samples obtained from control patients (n = 28) was 4.8 +/- 0.5 pg/ml; from patients with minimal-mild endometriosis (n = 24) was 27.5 +/- 2.6 pg/ml; and from patients with moderate-severe endometriosis (n = 21) was 530.2 +/- 65.1 pg/ml. Confluent mesothelial cells were incubated with human recombinant IL-1 alpha (0.01-100 IU/ml) or tumour necrosis factor (TNF)-alpha (0.01 to 100 ng/ml) for 2-24 h. IL-8 mRNA was detectable in non-treated cells, however both IL-1 alpha and TNF-alpha induced higher amounts of IL-8 mRNA in a dose- and time-dependent manner. Non-treated mesothelial cells in culture also produced and secreted IL-8 protein quantified by ELISA, but again higher concentrations were induced by IL-1 alpha and TNF-alpha treatment. In conclusion, we found that IL-8 concentrations were elevated in peritoneal fluids from women with endometriosis. Cultured mesothelial cells expressed cytokine-inducible IL-8 mRNA and secreted IL-8 protein. The regulated expression of this angiogenic factor may play a role in pathogenesis of endometriosis.
Arici
A
A
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06510, USA.
Tazuke
S I
SI
Attar
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E
Kliman
H J
HJ
Olive
D L
DL
D001202:Ascitic Fluid / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D015152:Blotting, Northern; D002478:Cells, Cultured; D004715:Endometriosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007118:Immunoassay; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018709:Statistics, Nonparametric
D016209:Interleukin-8; D012333:RNA, Messenger