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Lipopolysaccharide induces expression of genes encoding pro-inflammatory cytokines and the elastin-degrading enzyme, cathepsin S, in human cervical smooth-muscle cells.
- Source :
-
Journal of the Society for Gynecologic Investigation [J Soc Gynecol Investig] 2000 May-Jun; Vol. 7 (3), pp. 190-8. - Publication Year :
- 2000
-
Abstract
- Objective: Vaginal and amniotic infection with gram-negative bacteria is associated with preterm birth. We previously reported that human cervical smooth-muscle cells (CSMC) respond to pro-inflammatory cytokines by expressing enzymes that degrade the extracellular matrix. Our objective was to characterize the effects of lipopolysaccharide (LPS) from Escherichia coli (E coli), Bacteroides fragilis, (B frag)and Fusobacterium nucleatum (F nuc)on the expression of pro-inflammatory cytokines and the elastin-degrading enzyme, cathepsin S, in human CSMC.<br />Methods: Human CSMC were exposed to LPS and the expression of mRNAs encoding pro-inflammatory cytokines and cathepsin S, and selected matrix metalloproteinases (MMPs) was analyzed by Northern blotting. The effect of cytokine-neutralizing antibodies on LPS-induced cathepsin S mRNA expression also was determined.<br />Results: E coli LPS increased expression of cathepsin S 12.5-fold after 12 hours; MMP-1 and MMP-3 mRNAs also were increased 2.9- and 3.5-fold, respectively. Tumor necrosis factor (TNF)-alpha, interleukin (IL-1)alpha, and IL-1beta mRNAs were markedly up-regulated after 3 hours of LPS treatment. B frag and F nuc LPS also induced TNF-alpha and cathepsin S mRNAs. E coli LPS caused a sevenfold increase in TNF-alpha secretion after 5 to 8 hours. Antihuman TNF-alpha monoclonal antibody, but not a monoclonal antibody to the low-density lipoprotein receptor, reduced the LPS-induced increase in cathepsin S mRNA by 27%, whereas neutralizing antibodies against IL-1alpha and IL-1beta did not suppress the response. Human CSMC were shown to express the toll-like receptor (TLR-2) and TLR-4 genes, which mediate the action of LPS. TLR-2 mRNA was up-regulated by TNF-alpha.<br />Conclusion: CSMC respond to LPS with increased expression of pro-inflammatory cytokines and cathepsin S. Increases in cathepsin S mRNA result only in part from the rapid induction of TNF-alpha gene expression. TNF-alpha may also augment the CSMC response to LPS by increasing expression of the LPS signaling receptor, TLR-2, which probably directly mediates LPS action. These observations provide a mechanism by which gram-negative bacteria can precipitate cervical changes associated with preterm birth.
- Subjects :
- Cells, Cultured
Dactinomycin pharmacology
Escherichia coli
Female
Humans
Interleukin-1 genetics
Matrix Metalloproteinase 1 genetics
Matrix Metalloproteinase 3 genetics
Muscle, Smooth metabolism
Nucleic Acid Synthesis Inhibitors pharmacology
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor-alpha genetics
Cathepsins genetics
Cervix Uteri metabolism
Cytokines genetics
Gene Expression
Lipopolysaccharides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1071-5576
- Volume :
- 7
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of the Society for Gynecologic Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 10865188
- Full Text :
- https://doi.org/10.1016/s1071-5576(00)00054-x