Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in the human fallopian tube

OBJECTIVE: The fallopian tube is the site of fertilization and early embryonic growth and a common site of ectopic implantation. Although the factors responsible for early embryogenesis and implantation are incompletely understood, leukemia inhibitory factor may have an important role in early embry...

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Veröffentlicht in:American journal of obstetrics and gynecology 1996-12, Vol.175 (6), p.1611-1619
Hauptverfasser: Keltz, Martin D., Attar, Erkut, Buradagunta, Sumati, Olive, David L., Kliman, Harvey J., Arici, Aydin
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container_end_page 1619
container_issue 6
container_start_page 1611
container_title American journal of obstetrics and gynecology
container_volume 175
creator Keltz, Martin D.
Attar, Erkut
Buradagunta, Sumati
Olive, David L.
Kliman, Harvey J.
Arici, Aydin
description OBJECTIVE: The fallopian tube is the site of fertilization and early embryonic growth and a common site of ectopic implantation. Although the factors responsible for early embryogenesis and implantation are incompletely understood, leukemia inhibitory factor may have an important role in early embryonic development and implantation. We set out to evaluate the production and modulation of leukemia inhibitory factor in the fallopian tube. STUDY DESIGN: We first investigated leukemia inhibitory factor messenger ribonucleic acid levels in fallopian tubes. We then investigated leukemia inhibitory factor messenger ribonucleic acid and protein production in tubal epithelial and stromal cell cultures. RESULTS: Leukemia inhibitory factor messenger ribonucleic acid is expressed in the fallopian tube with only slight variation during the menstrual cycle; however, it is markedly elevated in association with ectopic pregnancy. The level is higher in the tubal mucosa than in the remaining layers and is higher in the more distal segments of the fallopian tube. Estradiol and progesterone did not modulate leukemia inhibitory factor expression in epithelial or stromal cell cultures. Interleukin-1α, tumor necrosis factor-α, and transforming growth factor-β enhanced leukemia inhibitory factor expression in epithelial and stromal cells, with transforming growth factor-β1 enhancing expression by fourfold in stromal cells. Epithelial cells secreted high levels of leukemia inhibitory factor compared with stromal cells (332 ± 89 vs 25 ± 42 pg/mg total protein). Yet stromal cells treated with transforming growth factor-β alone or in combination with epidermal growth factor and platelet-derived growth factor, as well as TNF-α alone or in combination with interleukin-1α enhanced secretion of leukemia inhibitory factor at or above the levels found with epithelial cells. CONCLUSIONS: We speculate that the high constitutive levels of leukemia inhibitory factor expressed in the ampullary portion of the fallopian tube may play a role in early embryonic development. Additionally, elevated expression with ectopic implantation and the marked induction of secretion in the tubal stroma by growth factors and cytokines suggest a link between inflammation, leukemia inhibitory factor, and tubal ectopic pregnancies. (Am J Obstet Gynecol 1996;175:1611-9.)
doi_str_mv 10.1016/S0002-9378(96)70114-X
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Although the factors responsible for early embryogenesis and implantation are incompletely understood, leukemia inhibitory factor may have an important role in early embryonic development and implantation. We set out to evaluate the production and modulation of leukemia inhibitory factor in the fallopian tube. STUDY DESIGN: We first investigated leukemia inhibitory factor messenger ribonucleic acid levels in fallopian tubes. We then investigated leukemia inhibitory factor messenger ribonucleic acid and protein production in tubal epithelial and stromal cell cultures. RESULTS: Leukemia inhibitory factor messenger ribonucleic acid is expressed in the fallopian tube with only slight variation during the menstrual cycle; however, it is markedly elevated in association with ectopic pregnancy. The level is higher in the tubal mucosa than in the remaining layers and is higher in the more distal segments of the fallopian tube. Estradiol and progesterone did not modulate leukemia inhibitory factor expression in epithelial or stromal cell cultures. Interleukin-1α, tumor necrosis factor-α, and transforming growth factor-β enhanced leukemia inhibitory factor expression in epithelial and stromal cells, with transforming growth factor-β1 enhancing expression by fourfold in stromal cells. Epithelial cells secreted high levels of leukemia inhibitory factor compared with stromal cells (332 ± 89 vs 25 ± 42 pg/mg total protein). Yet stromal cells treated with transforming growth factor-β alone or in combination with epidermal growth factor and platelet-derived growth factor, as well as TNF-α alone or in combination with interleukin-1α enhanced secretion of leukemia inhibitory factor at or above the levels found with epithelial cells. CONCLUSIONS: We speculate that the high constitutive levels of leukemia inhibitory factor expressed in the ampullary portion of the fallopian tube may play a role in early embryonic development. Additionally, elevated expression with ectopic implantation and the marked induction of secretion in the tubal stroma by growth factors and cytokines suggest a link between inflammation, leukemia inhibitory factor, and tubal ectopic pregnancies. 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Obstetrics ; Hormones - pharmacology ; Humans ; Interleukin-6 ; Leukemia Inhibitory Factor ; Lymphokines - genetics ; Lymphokines - metabolism ; Medical sciences ; Middle Aged ; Pregnancy ; Pregnancy, Ectopic - metabolism ; Pregnancy. Fetus. 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Although the factors responsible for early embryogenesis and implantation are incompletely understood, leukemia inhibitory factor may have an important role in early embryonic development and implantation. We set out to evaluate the production and modulation of leukemia inhibitory factor in the fallopian tube. STUDY DESIGN: We first investigated leukemia inhibitory factor messenger ribonucleic acid levels in fallopian tubes. We then investigated leukemia inhibitory factor messenger ribonucleic acid and protein production in tubal epithelial and stromal cell cultures. RESULTS: Leukemia inhibitory factor messenger ribonucleic acid is expressed in the fallopian tube with only slight variation during the menstrual cycle; however, it is markedly elevated in association with ectopic pregnancy. The level is higher in the tubal mucosa than in the remaining layers and is higher in the more distal segments of the fallopian tube. Estradiol and progesterone did not modulate leukemia inhibitory factor expression in epithelial or stromal cell cultures. Interleukin-1α, tumor necrosis factor-α, and transforming growth factor-β enhanced leukemia inhibitory factor expression in epithelial and stromal cells, with transforming growth factor-β1 enhancing expression by fourfold in stromal cells. Epithelial cells secreted high levels of leukemia inhibitory factor compared with stromal cells (332 ± 89 vs 25 ± 42 pg/mg total protein). Yet stromal cells treated with transforming growth factor-β alone or in combination with epidermal growth factor and platelet-derived growth factor, as well as TNF-α alone or in combination with interleukin-1α enhanced secretion of leukemia inhibitory factor at or above the levels found with epithelial cells. CONCLUSIONS: We speculate that the high constitutive levels of leukemia inhibitory factor expressed in the ampullary portion of the fallopian tube may play a role in early embryonic development. Additionally, elevated expression with ectopic implantation and the marked induction of secretion in the tubal stroma by growth factors and cytokines suggest a link between inflammation, leukemia inhibitory factor, and tubal ectopic pregnancies. (Am J Obstet Gynecol 1996;175:1611-9.)</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Blood Physiological Phenomena</subject><subject>Cells, Cultured</subject><subject>Culture Media</subject><subject>Cytokines - pharmacology</subject><subject>Diseases of mother, fetus and pregnancy</subject><subject>ectopic pregnancy</subject><subject>Epithelium - metabolism</subject><subject>fallopian tube</subject><subject>Fallopian Tubes - cytology</subject><subject>Fallopian Tubes - metabolism</subject><subject>Fallopian Tubes - physiology</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Growth Inhibitors - genetics</subject><subject>Growth Inhibitors - metabolism</subject><subject>Growth Substances - pharmacology</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Hormones - pharmacology</subject><subject>Humans</subject><subject>Interleukin-6</subject><subject>Leukemia Inhibitory Factor</subject><subject>Lymphokines - genetics</subject><subject>Lymphokines - metabolism</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pregnancy</subject><subject>Pregnancy, Ectopic - metabolism</subject><subject>Pregnancy. Fetus. 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Andrology. Obstetrics</topic><topic>Hormones - pharmacology</topic><topic>Humans</topic><topic>Interleukin-6</topic><topic>Leukemia Inhibitory Factor</topic><topic>Lymphokines - genetics</topic><topic>Lymphokines - metabolism</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pregnancy</topic><topic>Pregnancy, Ectopic - metabolism</topic><topic>Pregnancy. Fetus. Placenta</topic><topic>RNA, Messenger - metabolism</topic><topic>Stromal Cells - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Keltz, Martin D.</creatorcontrib><creatorcontrib>Attar, Erkut</creatorcontrib><creatorcontrib>Buradagunta, Sumati</creatorcontrib><creatorcontrib>Olive, David L.</creatorcontrib><creatorcontrib>Kliman, Harvey J.</creatorcontrib><creatorcontrib>Arici, Aydin</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of obstetrics and gynecology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Keltz, Martin D.</au><au>Attar, Erkut</au><au>Buradagunta, Sumati</au><au>Olive, David L.</au><au>Kliman, Harvey J.</au><au>Arici, Aydin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in the human fallopian tube</atitle><jtitle>American journal of obstetrics and gynecology</jtitle><addtitle>Am J Obstet Gynecol</addtitle><date>1996-12-01</date><risdate>1996</risdate><volume>175</volume><issue>6</issue><spage>1611</spage><epage>1619</epage><pages>1611-1619</pages><issn>0002-9378</issn><eissn>1097-6868</eissn><coden>AJOGAH</coden><abstract>OBJECTIVE: The fallopian tube is the site of fertilization and early embryonic growth and a common site of ectopic implantation. Although the factors responsible for early embryogenesis and implantation are incompletely understood, leukemia inhibitory factor may have an important role in early embryonic development and implantation. We set out to evaluate the production and modulation of leukemia inhibitory factor in the fallopian tube. STUDY DESIGN: We first investigated leukemia inhibitory factor messenger ribonucleic acid levels in fallopian tubes. We then investigated leukemia inhibitory factor messenger ribonucleic acid and protein production in tubal epithelial and stromal cell cultures. RESULTS: Leukemia inhibitory factor messenger ribonucleic acid is expressed in the fallopian tube with only slight variation during the menstrual cycle; however, it is markedly elevated in association with ectopic pregnancy. The level is higher in the tubal mucosa than in the remaining layers and is higher in the more distal segments of the fallopian tube. Estradiol and progesterone did not modulate leukemia inhibitory factor expression in epithelial or stromal cell cultures. Interleukin-1α, tumor necrosis factor-α, and transforming growth factor-β enhanced leukemia inhibitory factor expression in epithelial and stromal cells, with transforming growth factor-β1 enhancing expression by fourfold in stromal cells. Epithelial cells secreted high levels of leukemia inhibitory factor compared with stromal cells (332 ± 89 vs 25 ± 42 pg/mg total protein). Yet stromal cells treated with transforming growth factor-β alone or in combination with epidermal growth factor and platelet-derived growth factor, as well as TNF-α alone or in combination with interleukin-1α enhanced secretion of leukemia inhibitory factor at or above the levels found with epithelial cells. CONCLUSIONS: We speculate that the high constitutive levels of leukemia inhibitory factor expressed in the ampullary portion of the fallopian tube may play a role in early embryonic development. Additionally, elevated expression with ectopic implantation and the marked induction of secretion in the tubal stroma by growth factors and cytokines suggest a link between inflammation, leukemia inhibitory factor, and tubal ectopic pregnancies. (Am J Obstet Gynecol 1996;175:1611-9.)</abstract><cop>Philadelphia, PA</cop><pub>Mosby, Inc</pub><pmid>8987949</pmid><doi>10.1016/S0002-9378(96)70114-X</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult
Biological and medical sciences
Blood Physiological Phenomena
Cells, Cultured
Culture Media
Cytokines - pharmacology
Diseases of mother, fetus and pregnancy
ectopic pregnancy
Epithelium - metabolism
fallopian tube
Fallopian Tubes - cytology
Fallopian Tubes - metabolism
Fallopian Tubes - physiology
Female
Gene Expression Regulation
Growth Inhibitors - genetics
Growth Inhibitors - metabolism
Growth Substances - pharmacology
Gynecology. Andrology. Obstetrics
Hormones - pharmacology
Humans
Interleukin-6
Leukemia Inhibitory Factor
Lymphokines - genetics
Lymphokines - metabolism
Medical sciences
Middle Aged
Pregnancy
Pregnancy, Ectopic - metabolism
Pregnancy. Fetus. Placenta
RNA, Messenger - metabolism
Stromal Cells - metabolism
title Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in the human fallopian tube
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