Tags

Type your tag names separated by a space and hit enter

Cytokines regulate matrix metalloproteinases in human uterine endometrial fibroblast cells through a mechanism that does not involve increases in extracellular matrix metalloproteinase inducer.
Am J Reprod Immunol. 2006 Sep; 56(3):201-14.AJ

Abstract

PROBLEM

Endometriosis is the presence of ectopic uterine endometrial tissue in the peritoneal cavity. Peritoneal fluid samples of women with endometriosis show elevated interleukin-1 (IL-1)beta, tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta(1) levels, indicating that an altered immune system may play an important role in the pathogenesis of endometriosis. The invasion of ectopic endometrium into peritoneal mesothelium requires matrix metalloproteinases (MMPs) for tissue remodeling. Several MMPs are differentially expressed in human uterine endometrium with menstrual endometrium showing the highest level of expression. MMPs are stimulated by cytokines and also by the protein Extracellular Matrix Metalloproteinase Inducer (EMMPRIN).

METHOD OF STUDY

To determine the role of cytokines in ectopic endometrial invasion, we investigated whether cytokines could regulate MMP production by endometrial fibroblast cells and whether this stimulation occurred through an effect on EMMPRIN expression. Human uterine fibroblasts (HUF) were treated with IL-1beta, TGF-beta(1) and TNF-alpha in a dose dependent and time dependent manner (C, 0.1, 1, 10 ng/mL IL-1beta or TGF-beta(1); C, 2, 10, 50 ng/mL TNF-alpha) for 0, 6, 12, and 24 hr. Cell conditioned medium samples were collected and concentrated at each timepoint for immunoblot analysis. Cellular RNA was collected for real time PCR analysis of MMPs-1, -2, -3 and EMMPRIN mRNA levels.

RESULTS

Our results showed that IL-1beta stimulated MMP-1 protein secretion and mRNA levels in a time dependent manner (P < 0.05), MMP-2 mRNA in a time dependent manner and MMP-3 in a time and dose dependent manner. TNF-alpha stimulated MMP-1 and -3 protein secretion in a time dependent manner and stimulated MMP-1, -2 and -3 mRNA levels in a time dependent manner (P < 0.05). Neither IL-1beta nor TNF-alpha treatment affected MMP-2 protein secretion. TGF-beta(1) inhibited MMP-1 and MMP-2 mRNAs at the highest treatment dose after 24 hr but there was no effect on protein secretion. TGF-beta(1) exerted no effect on MMP-3 mRNA or protein secretion (P < 0.05). Neither of the cytokines affected EMMPRIN protein or mRNA levels but the 10 ng/mL TGF-beta(1) treatment did cause a reduction in EMMPRIN mRNA levels.

CONCLUSIONS

These data show that elevated cytokines may play a role in the establishment of ectopic endometrium in the peritoneal cavity by stimulating MMPs to remodel the mesothelial lining of the peritoneum thus allowing for tissue invasion. The stimulation of MMPs by cytokines occurred without any change in EMMPRIN expression whereas the inhibitory effect of TGF-beta(1) involved a reduction in EMMPRIN mRNA levels.

Authors+Show Affiliations

Department of Animal Sciences, University of Illinois, Urbana, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16911716

Citation

Braundmeier, Andrea G., and Romana A. Nowak. "Cytokines Regulate Matrix Metalloproteinases in Human Uterine Endometrial Fibroblast Cells Through a Mechanism That Does Not Involve Increases in Extracellular Matrix Metalloproteinase Inducer." American Journal of Reproductive Immunology (New York, N.Y. : 1989), vol. 56, no. 3, 2006, pp. 201-14.
Braundmeier AG, Nowak RA. Cytokines regulate matrix metalloproteinases in human uterine endometrial fibroblast cells through a mechanism that does not involve increases in extracellular matrix metalloproteinase inducer. Am J Reprod Immunol. 2006;56(3):201-14.
Braundmeier, A. G., & Nowak, R. A. (2006). Cytokines regulate matrix metalloproteinases in human uterine endometrial fibroblast cells through a mechanism that does not involve increases in extracellular matrix metalloproteinase inducer. American Journal of Reproductive Immunology (New York, N.Y. : 1989), 56(3), 201-14.
Braundmeier AG, Nowak RA. Cytokines Regulate Matrix Metalloproteinases in Human Uterine Endometrial Fibroblast Cells Through a Mechanism That Does Not Involve Increases in Extracellular Matrix Metalloproteinase Inducer. Am J Reprod Immunol. 2006;56(3):201-14. PubMed PMID: 16911716.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytokines regulate matrix metalloproteinases in human uterine endometrial fibroblast cells through a mechanism that does not involve increases in extracellular matrix metalloproteinase inducer. AU - Braundmeier,Andrea G, AU - Nowak,Romana A, PY - 2006/8/17/pubmed PY - 2006/10/18/medline PY - 2006/8/17/entrez SP - 201 EP - 14 JF - American journal of reproductive immunology (New York, N.Y. : 1989) JO - Am. J. Reprod. Immunol. VL - 56 IS - 3 N2 - PROBLEM: Endometriosis is the presence of ectopic uterine endometrial tissue in the peritoneal cavity. Peritoneal fluid samples of women with endometriosis show elevated interleukin-1 (IL-1)beta, tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta(1) levels, indicating that an altered immune system may play an important role in the pathogenesis of endometriosis. The invasion of ectopic endometrium into peritoneal mesothelium requires matrix metalloproteinases (MMPs) for tissue remodeling. Several MMPs are differentially expressed in human uterine endometrium with menstrual endometrium showing the highest level of expression. MMPs are stimulated by cytokines and also by the protein Extracellular Matrix Metalloproteinase Inducer (EMMPRIN). METHOD OF STUDY: To determine the role of cytokines in ectopic endometrial invasion, we investigated whether cytokines could regulate MMP production by endometrial fibroblast cells and whether this stimulation occurred through an effect on EMMPRIN expression. Human uterine fibroblasts (HUF) were treated with IL-1beta, TGF-beta(1) and TNF-alpha in a dose dependent and time dependent manner (C, 0.1, 1, 10 ng/mL IL-1beta or TGF-beta(1); C, 2, 10, 50 ng/mL TNF-alpha) for 0, 6, 12, and 24 hr. Cell conditioned medium samples were collected and concentrated at each timepoint for immunoblot analysis. Cellular RNA was collected for real time PCR analysis of MMPs-1, -2, -3 and EMMPRIN mRNA levels. RESULTS: Our results showed that IL-1beta stimulated MMP-1 protein secretion and mRNA levels in a time dependent manner (P < 0.05), MMP-2 mRNA in a time dependent manner and MMP-3 in a time and dose dependent manner. TNF-alpha stimulated MMP-1 and -3 protein secretion in a time dependent manner and stimulated MMP-1, -2 and -3 mRNA levels in a time dependent manner (P < 0.05). Neither IL-1beta nor TNF-alpha treatment affected MMP-2 protein secretion. TGF-beta(1) inhibited MMP-1 and MMP-2 mRNAs at the highest treatment dose after 24 hr but there was no effect on protein secretion. TGF-beta(1) exerted no effect on MMP-3 mRNA or protein secretion (P < 0.05). Neither of the cytokines affected EMMPRIN protein or mRNA levels but the 10 ng/mL TGF-beta(1) treatment did cause a reduction in EMMPRIN mRNA levels. CONCLUSIONS: These data show that elevated cytokines may play a role in the establishment of ectopic endometrium in the peritoneal cavity by stimulating MMPs to remodel the mesothelial lining of the peritoneum thus allowing for tissue invasion. The stimulation of MMPs by cytokines occurred without any change in EMMPRIN expression whereas the inhibitory effect of TGF-beta(1) involved a reduction in EMMPRIN mRNA levels. SN - 1046-7408 UR - https://www.unboundmedicine.com/medline/citation/16911716/Cytokines_regulate_matrix_metalloproteinases_in_human_uterine_endometrial_fibroblast_cells_through_a_mechanism_that_does_not_involve_increases_in_extracellular_matrix_metalloproteinase_inducer_ L2 - https://doi.org/10.1111/j.1600-0897.2006.00418.x DB - PRIME DP - Unbound Medicine ER -