Regulation of interleukin-8 synthesis in human lower uterine segment fibroblasts by cytokines and growth factors.
OBJECTIVE
To investigate the influence of lipopolysaccharide, cytokines, growth factors, and progesterone on the synthesis of interleukin-8 by human lower uterine segment fibroblasts.


METHODS
Fibroblasts derived from a lower uterine segment biopsy specimen obtained from a woman undergoing elective cesarean delivery at term were exposed to lipopolysaccharide, interleukin-1beta, transforming growth factor-beta(1), platelet-derived growth factor-AB, and combinations of these substances. All experiments were performed in the absence and presence of progesterone. The concentration of interleukin-8 in the culture medium was determined by enzyme immunoassay after 24 hours.


RESULTS
Compared with controls (0.71 +/- 0.04 ng interleukin-8/10(6) cells), fibroblasts exposed to lipopolysaccharide, transforming growth factor-beta(1), or platelet-derived growth factor-AB exhibited no increase, or at most, only a minor but significant increase, in interleukin-8 secretion. Incubation with interleukin-1beta led to a moderate increase, whereas the combinations interleukin-1beta/transforming growth factor-beta(1) (105.0 +/- 7.5 ng interleukin-8/10(6) cells) and interleukin-1beta/platelet-derived growth factor-AB (387.3 +/- 25.6 ng interleukin-8/10(6) cells) increased interleukin-8 secretion dramatically. No further increase was observed with the combination interleukin-1beta/platelet-derived growth factor-AB/transforming growth factor-beta(1). When progesterone was added, interleukin-8 secretion decreased significantly by 16-34%, depending on the stimulator, or did not change.


CONCLUSIONS
The findings indicate that interleukin-8 secretion by human lower uterine segment fibroblasts in vitro is upregulated by interleukin-1beta, transforming growth factor-beta(1), and platelet-derived growth factor-AB in a synergistic fashion. Because interleukin-8 mediates the invasion of neutrophils into the cervical stroma, this may be an important mechanism controlling cervical dilatation during parturition.
Winkler
M
M
Department of Obstetrics and Gynecology, University Hospital, Technical University, Aachen, Germany. mwinkler@post.klinikum.rwth-aachen.de
Rath
W
W
Fischer
D C
DC
van de Leur
E
E
Haubeck
H
H
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D011247:Pregnancy; D014599:Uterus / Q000166:cytology*
D016207:Cytokines; D006133:Growth Substances; D016209:Interleukin-8