Interleukin-8 induces proliferation of endometrial stromal cells: a potential autocrine growth factor.
Proliferation of endometrium is dependent on sex steroid hormones, but specific growth factors are likely to play an important role in regulating this process. A number of cytokines and growth factors are synthesized in the endometrium in response to sex steroid hormones and act to regulate endometrial function. Endometrial cells produce interleukin-8 (IL-8) both in vivo and in vitro. We hypothesized that IL-8, a neutrophil chemoattractant/activating factor and a potent angiogenic agent that has been shown to stimulate growth in other cell types, may directly stimulate proliferation of endometrial cells. We first investigated the effect of IL-8 and mouse antihuman-IL-8 neutralizing antibody on endometrial stromal cell proliferation using both a colorimetric assay and thymidine uptake. We then investigated the modulation of endometrial stromal cell IL-8 production and proliferation by antisense oligonucleotides specific for IL-8. There was a concentration-dependent increase of cell proliferation with IL-8 (2-fold at 1 ng/mL; P < 0.01 between control and concentrations above 0.01 ng/mL) and a concentration-dependent inhibition of cell proliferation with anti-IL-8 antibody (to 30% of the control at 1 microg/mL; P < 0.01 between control and concentrations above 0.1 microg/mL). IL-8 antisense oligonucleotide treatment decreased IL-8 production by endometrial stromal cells in culture as well as cell proliferation when it is compared with scrambled (nonsense) oligonucleotide treatment (P < 0.01). Addition of IL-8 (1 ng/mL) reversed the proliferation inhibitory effect of IL-8 antisense oligonucleotides. We propose that IL-8 may act as an autocrine growth factor in the endometrium, and suggest that it may also play a role in the pathogenesis of endometriosis.
Arici
A
A
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. Aydin.Arici@Yale.edu
Seli
E
E
Zeyneloglu
H B
HB
Senturk
L M
LM
Oral
E
E
Olive
D L
DL
D000328:Adult; D000937:Antigen-Antibody Reactions; D019898:Autocrine Communication; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology*; D005260:Female; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology / Q000502:physiology*; D016376:Oligonucleotides, Antisense; D017154:Stromal Cells / Q000502:physiology
D006133:Growth Substances; D016209:Interleukin-8; D016376:Oligonucleotides, Antisense