title: Tumor necrosis factor-alpha and interleukin-1beta regulate interleukin-8 expression in third trimester decidual cells: implications for the genesis of chorioamnionitis.
abstract: Chorioamnionitis is associated with intense neutrophil infiltration of the decidua. We therefore determined whether chorioamnionitis enhances decidual interleukin-8 (IL-8) expression and examined cytokine-regulated decidual IL-8 expression. Decidua from chorioamnionitis-complicated pregnancies, but not term controls, displayed marked IL-8 immunohistochemical staining and a dense neutrophil infiltrate. Reverse transcriptase-polymerase chain reaction of microdissected decidual cells identified IL-8 mRNA, confirming decidual synthesis of IL-8. Confluent leukocyte-free term decidual cells were primed with 10(-8) mol/L estradiol (E2) or E2 + 10(-7) mol/L medroxyprogesterone acetate to mimic the steroidal milieu of pregnancy. Compared with cultures maintained in E2 alone, E2 + medroxyprogesterone acetate neither significantly affected IL-8 levels nor altered the response to the cytokines. The addition of 1.0 ng/ml tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1beta) increased IL-8 secretion levels by 236.6 +/- 51.4- and 1062.6 +/- 254.3-fold, respectively (n = 8, mean +/- SEM, P < 0.05), as measured by enzyme-linked immunosorbent assay. Concentration-response studies revealed that 0.01 ng/ml TNF-alpha and IL-1beta elevated IL-8 output by 10- and 100-fold, respectively. Western blotting confirmed these results, and quantitative reverse transcriptase-polymerase chain reaction demonstrated parallel changes in mRNA levels. In conclusion, IL-8 is strongly expressed in term decidua during chorioamnionitis, and TNF-alpha and IL-1beta enhance IL-8 expression in term decidual cells, suggesting that these cytokines are important regulators of chorioamnionitis-related decidual neutrophil infiltration.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, Room 335 FMB P.O. Box 208063 New Haven, CT. Frederick.Schatz@yale.edu.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lockwood
authors.forename: Felice
authors.initials: F
authors.lastname: Arcuri
authors.forename: Paolo
authors.initials: P
authors.lastname: Toti
authors.forename: Claudio De
authors.initials: CD
authors.lastname: Felice
authors.forename: Graciela
authors.initials: G
authors.lastname: Krikun
authors.forename: Seth
authors.initials: S
authors.lastname: Guller
authors.forename: Lynn F
authors.initials: LF
authors.lastname: Buchwalder
authors.forename: Frederick
authors.initials: F
authors.lastname: Schatz
mesh_terms: D002478:Cells, Cultured; D002821:Chorioamnionitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003656:Decidua / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology / Q000502:physiology*; D016209:Interleukin-8 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
chemical_list: D053583:Interleukin-1beta; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D017258:Medroxyprogesterone Acetate