Interleukin-8 expression and modulation in human preovulatory follicles and ovarian cells.
Just before the time of ovulation, the number of neutrophils increases markedly in the thecal layer of the leading follicle. A preovulatory rise in chemotactic activity for neutrophils in human follicular fluid has also been detected. We hypothesized that interleukin-8 (IL-8), a neutrophil chemoattractant/activating factor and a potent angiogenic agent, may be an important modulator of leukocyte chemotaxis in ovulatory function. In this regard we investigated the expression and modulation of IL-8 in human follicular fluid samples from patients undergoing in vitro fertilization-embryo transfer therapy and in ovarian stromal and granulosa-lutein cell cultures. The concentration of IL-8 in pre-hCG follicular fluid samples (n = 4) was 16 +/- 12 (mean +/- SEM) pg/ml, and that in post-hCG samples (n = 101) was 262 +/- 45 pg/ml (P = 0.001). In post-hCG samples, the concentration of IL-8 in an individual follicle correlated with the size of that follicle (r = 0.61; P = 0.02). We also observed a correlation between serum IL-8 levels (22 +/- 3 pg/ml) and follicular fluid levels (303 +/- 143 pg/ml), with a 14-fold gradient (r = 0.71; P = 0.01) in 11 patients tested for both. IL-8 messenger RNA (mRNA) and the protein were expressed constitutively in ovarian stromal cell cultures, and the level was increased by IL-1 alpha and tumor necrosis factor-alpha in a time- and concentration-dependent manner. hCG and LH induced higher levels of IL-8 mRNA expression and protein production. Granulosalutein cells also expressed IL-8 mRNA and protein, and the levels were increased by IL-1 alpha and tumor necrosis factor-alpha. Importantly, progesterone suppressed both basal and IL-1 alpha-stimulated IL-8 expression in stromal and granulosa-lutein cell types. In summary, we found that IL-8 levels are elevated in periovulatory follicular fluid, and both granulosa-lutein and ovarian stromal cells express the mRNA and produce the protein. The modulation of IL-8 in these cell cultures by steroid and trophic hormones suggests that IL-8 may play an important role in the physiology of ovulation, such as timely follicular rupture and neovascularization of the corpus luteum.
Arici
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A
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. Aydin.Arici@yale.edu
Oral
E
E
Bukulmez
O
O
Buradagunta
S
S
Engin
O
O
Olive
D L
DL
D000328:Adult; D001483:Base Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism; D005498:Follicular Phase; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D006080:Ovarian Follicle / Q000378:metabolism*; D010053:Ovary / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology; D017154:Stromal Cells / Q000378:metabolism
D016207:Cytokines; D006728:Hormones; D016209:Interleukin-8; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D013256:Steroids