Origin of cervical collagenase during parturition

Osmers, R.; Rath, Werner; Adelmanngrill, Bc; Fittkow, Cordula; Kuloczik, M; Szeverényi, M; Tschesche, Harald; Kuhn, Walther

doi:10.1016/0020-7292(93)90794-w

Cited by 48 publications

(66 citation statements)

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“…Moreover, the expression of these genes was markedly up-regulated in response to TNF-␣ and IL-1␤, cytokines that may participate in the normal process of cervical ripening or the premature remodeling of the cervix associated with preterm labor. 4,5 We also obtained preliminary evidence for CSMC expression of MMP-13, an enzyme that degrades fibrillar collagens and also activates MMP-9 (unpublished observations). The abundance of MMP-13 mRNA was much lower than that of MMP-1, -3, and -9 mRNAs but, like these other MMP transcripts, MMP-13 message levels in the CSMC were increased by cytokine treatment.…”

Section: Discussionmentioning

confidence: 68%

See 1 more Smart Citation

Pro-Inflammatory Cytokines Induce Expression of Matrix-Metabolizing Enzymes in Human Cervical Smooth Muscle Cells

Watari

DiSanto

et al. 1999

The American Journal of Pathology

162

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The process of cervical ripening has been likened to an inflammatory reaction associated with the catabolism of cervical extracellular matrix by enzymes released from infiltrating leukocytes. We hypothesized that smooth muscle cells in the cervix also participate in this process and that pro-inflammatory cytokines act on cervical smooth muscle cells (CSMC) to provoke the expression of matrix-degrading enzymes. We treated primary cultures of human CSMC with tumor necrosis factor-␣ (TNF-␣) and examined expression of the elastinolytic enzyme , cathepsin S, the collagen metabolizing matrix metalloproteinases (MMP)-1 , -3 , -9 , and the tissue inhibitor of metalloproteinase (TIMP)-1 and -2. A time course analysis revealed that 10 ng/ml of TNF-␣ induced cathepsin S, MMP-1 , -3 , and -9 mRNA expression with the maximal response observed after 24 -48 hours. TNF-␣ induced cathepsin S , MMP-1 , -3 , and -9 mRNA expression in a dose-dependent manner: the maximal effect was observed at a concentration of 10 ng/ml , with appreciable increases observed at concentrations of 0.1 to 1.0 ng/ml. In contrast , TIMP-1 and -2 mRNAs were not significantly increased by TNF-␣ treatment. Interleukin-1␤ produced a pattern of gene expression in the CSMC similar to that observed following TNF-␣ treatment. Western blot analysis and zymography confirmed the induction of proMMP-1 , -3 , and -9 in response to TNF-␣, but MMP-2 immunoreactivity and zymographic activity were unaffected. TNF-␣ increased secretion of procathepsin S , but did not affect TIMP-1 and reduced TIMP-2 production. We conclude that CSMC are targets of pro-inflammatory cytokines, which induce a repertoire of enzymes capable of degrading the cervical extracellular matrix. The induction of these enzymes may facilitate the normal ripening of the cervix at term and participate in the The human cervix is composed primarily of connective tissue consisting mainly of fibrillar collagens, elastin, and glycosaminoglycans.

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Section: Discussionmentioning

confidence: 68%

“…3 The profound remodeling of the cervical extracellular matrix occurs coincidentally with a dramatic influx of white blood cells. 4,5 Thus, the process of cervical ripening has been likened to an inflammatory response.…”

mentioning

confidence: 99%

Pro-Inflammatory Cytokines Induce Expression of Matrix-Metabolizing Enzymes in Human Cervical Smooth Muscle Cells

Watari

DiSanto

et al. 1999

The American Journal of Pathology

162

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“…Polymorphonuclear leukocytes and macrophages migrate from blood vessels and accumulate in the cervix uteri before parturition (Stygar et al 2001). The hypothesis of the role of inflammatory cells in cervical ripening (Liggins 1981) has been supported by studies showing that cervical collagenases at parturition originate not only from resident fibroblasts of the cervical stroma but also from leukocytes invading the cervix (Osmers et al 1992). In a previous study, we could show that the matrix metalloproteinase (MMP)-9 is present in the invading leukocytes of the human cervix (Stygar et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Studies on estrogen receptor (ER) α and β responses on gene regulation in peripheral blood leukocytes in vivo using selective ER agonists

Stygar¹,

Masironi²,

Eriksson³

et al. 2007

Journal of Endocrinology

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Major reproductive events such as menstruation, ovulation, implantation, and cervical ripening are characterized by an increased number of invading leukocytes in the tissues. Sex steroid hormones, particularly estrogens, play an important role in these dynamic changes in the female reproductive tract. Estrogens have also been implicated in the pathogenesis of many common pathological conditions associated with leukocyte infiltration and immunological dysfunction, such as autoimmune diseases and atherosclerosis. Although the two estrogen receptor (ER) subtypes, ERa and ERb, have been found in different leukocyte populations in tissues and in peripheral blood, there is still very little known about functional activity and importance of ERs in blood cells. To elucidate the different roles for ERa and ERb in peripheral blood leukocytes, we used microarray gene expression profiling of rat peripheral blood leukocytes subjected to in vivo treatment with estradiol (E 2 ), the selective ERa agonist 4,4 0 ,4 00 -(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), and the selective ERb agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN). We report the identification of genes that were commonly regulated by E 2 , PPT, and DPN, and genes that were regulated either by the ERa or ERb agonist. Further confirmatory analyses of the selected regulated genes 12-lipoxygenase, fibulin-1, furin, and calgranulin B are also presented. These results were then compared with those from the uterine tissue of the same animals. Our study demonstrates that peripheral blood leukocytes are responsive to estrogens. E 2 and selective ERa and ERb agonists regulate a number of genes that may contribute to inflammation and remodeling of the extracellular matrix.

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“…Cervical stromal fibroblasts and smooth muscle cells were identified as main sources of MMP-2, but MMP-9 protein was localized exclusively in invading leukocytes (Stygar et al, 2002). There are also reports showing that migrating leukocytes secrete collagenases that could play an important role in tissue remodeling during cervical ripening (Osmers et al, 1992). These data indicate the involvement of invading leukocytes in the cervical ripening process.…”

Section: Cervical Ripening and Parturitionmentioning

confidence: 96%

“…It has been suggested that leukocytes could be responsible for the ripening of the cervix at term and these leukocytes express ERs (Junqueira et al, 1980;Osmers et al, 1992;Sahlin et al, 2008;Wang et al, 2001). Cervical ripening includes an inflammatory type of process and thus there is an infiltration of leukocytes.…”

Section: Cervical Ripening and Parturitionmentioning

confidence: 99%

Estrogen Receptors in Leukocytes - Possible Impact on Inflammatory Processes in the Female Reproductive System

Selvanesan¹

2011

Update on Mechanisms of Hormone Action - Focus on Metabolism, Growth and Reproduction

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Origin of cervical collagenase during parturition

Cited by 48 publications

References 0 publications

Pro-Inflammatory Cytokines Induce Expression of Matrix-Metabolizing Enzymes in Human Cervical Smooth Muscle Cells

Pro-Inflammatory Cytokines Induce Expression of Matrix-Metabolizing Enzymes in Human Cervical Smooth Muscle Cells

Studies on estrogen receptor (ER) α and β responses on gene regulation in peripheral blood leukocytes in vivo using selective ER agonists

Estrogen Receptors in Leukocytes - Possible Impact on Inflammatory Processes in the Female Reproductive System

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