Regulation of interleukin-8 synthesis in human lower uterine segment fibroblasts by cytokines and growth factors
- 1 April 2000
- journal article
- Published by Wolters Kluwer Health
- Vol. 95 (4) , 584-588
- https://doi.org/10.1016/s0029-7844(99)00614-6
Abstract
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-1β, transforming growth factor-β1, 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-8/106 cells), fibroblasts exposed to lipopolysaccharide, transforming growth factor-β1, 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-1β led to a moderate increase, whereas the combinations interleukin-1β/transforming growth factor-β1 (105.0 ± 7.5 ng interleukin-8/106 cells) and interleukin-1β/platelet-derived growth factor-AB (387.3 ± 25.6 ng interleukin-8/106 cells) increased interleukin-8 secretion dramatically. No further increase was observed with the combination interleukin-1β/platelet-derived growth factor-AB/transforming growth factor-β1. When progesterone was added, interleukin-8 secretion decreased significantly by 16–34%, depending on the stimulator, or did not change. Conclusion: The findings indicate that interleukin-8 secretion by human lower uterine segment fibroblasts in vitro is upregulated by interleukin-1β, transforming growth factor-β1, 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.Keywords
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