Binding of interleukin-8 to heparan sulphate enhances cervical maturation in rabbits

Abstract

Cervical ripening is a cytokine-trigged process with substantial remodelling of the cervical extracellular matrix. Interleukin-8 (IL-8) is an important cytokine in cervical maturation. Glycosaminoglycans are also included in this process, but their role in not clearly understood. The effects of heparan sulphate (HS), hyaluronic acid (HA), IL-8, HS ⍣ IL-8 and HA ⍣ IL-8 on biochemical properties of the cervix were examined in non-pregnant rabbits. The changes in vascular pattern with collagen structure of the cervices and immunohistochemical studies, together with the relative collagen concentrations, were determined. A reduction in relative collagen concentration was significant after HS ⍣ IL-8 , IL-8 and HA ⍣ IL-8 treatment (all P < 0.0001). Gel electrophoresis analysis showed that IL-8 bound preferentially to HS than to HA. Neutrophils were significantly increased in number (P < 0.0001) and located predominantly beneath the glandular epithelium and around the blood vessels after HS ⍣ IL-8 treatment. HS ⍣ IL-8 treatment caused cervices to increase their water content and become oedematous. The collagen fibres were considerably dissociated, the interfibrillar spaces markedly dilated, and the blood vessels notably increased and dilated. We conclude that binding to HS enhances the activity of IL-8 in inducing cervical maturation. Key words: cervical maturation/heparan sulphate/hyaluronic acid/interleukin-8/neutrophil activation IntroductionThe non-pregnant cervix is a fibrous structure which undergoes modifications during pregnancy to allow sufficient softening and growth for the passage of the fetus at birth (Harkness and Harkness, 1959;Friedman, 1980;Calder, 1981;Fitzpatrick, 1981). It is well established that the transformation of the uterine cervix to a soft and compliant structure during pregnancy is crucial for a normal delivery. This ripening process can be explained mainly in terms of connective tissue biology (Huszar and Walsh, 1991). Investigations of the structural alterations of cervical connective tissue during pregnancy and labour have focused predominantly on quantitative changes of the collagen content and the role of collagen-degraded enzymes (Ito et al., 1979;Danforth, 1980;Uldbjerg et al., 1983). However, there are strong indications that other macromolecular components of the cervix, such as proteoglycans (PG), may also be involved (von Maillot et al., 1979;Kitamura et al., 1980). PG are core proteins with covalently attached glycosaminoglycan (GAG) chains (Ruoslahti, 1988). In addition to heparin/ heparan sulphate (HS), chondroitin sulphate/dermatan sulphate, keratan sulphate and hyaluronic acid (HA) have also been isolated from the human cervix (von Maillot et al., 1979;Cabrol et al., 1980;Kitamura et al., 1980;Uldbjerg et al., 1983). A marked increase in the GAG content of the cervix during late pregnancy has been demonstrated in rats, rabbits, sheep and humans (Danforth et al., 1974;Golichowski et al., © European Society of Human Reproduction and Embryology 261 1980; Fosang et al., 1984;Mara...

Upregulation of interleukin-8 and polarized epithelial expression of interleukin-8 receptor a in ovarian carcinomas

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4‐Methylumbelliferone inhibits hyaluronate synthesis in human uterine cervical fibroblasts

“…For example, increasing hyaluronate contributes to collagenous framework loosening and to the increase in the water content of the human uterine cervix at term 3 . In addition, hyaluronate stimulates the production of IL‐1 and ‐8, which promotes collagenase production and results in rapid cervical ripening 15,16 . Further studies of hyaluronate metabolism may help to elucidate how hyaluronate exerts its effect and how cervical ripening can be controlled during parturition.…”

“…3 In addition, hyaluronate stimulates the production of IL-1 and -8, which promotes collagenase production and results in rapid cervical ripening. 15,16 Further studies of hyaluronate metabolism may help to elucidate how hyaluronate exerts its effect and how cervical ripening can be controlled during parturition.…”

Aspectos morfológicos da junção escamo-colunar de ratas em estro permanente e tratadas com associação de estrogênio e glicocorticóide

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