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Cytokine2019; 123; 154767; doi: 10.1016/j.cyto.2019.154767

Effect of proinflammatory cytokines on endometrial collagen and metallopeptidase expression during the course of equine endometrosis.

Abstract: Equine endometrosis (endometrial fibrosis) is a degenerative chronic process that occurs in the uterus of the mare and disturbs proper endometrial function. Fibrosis is attributed to excessive deposition of extracellular matrix (ECM) components. The turnover of ECM is mediated by matrix metallopeptidases (MMP). Previously, it was shown that cytokines modulate MMP expression in other tissues and may regulate fibrosis indirectly by attracting inflammatory cells to the site of inflammation and directly on various tissues. However, the regulation of MMP expression in equine endometrosis is still relatively unknown. Thus, our aim was to determine if interleukin (IL)-1β and IL-6 regulate ECM, MMPs, or their inhibitors (TIMPs) and whether this regulation differs during endometrosis in the mare. Endometrial fibrosis was divided into four categories according to severity: I (no degenerative changes), IIA (mild degenerative changes), IIB (moderate degenerative changes) and III (severe degenerative changes) according to Kenney and Doig classification. Endometrial explants (n = 5 for category I, IIA, IIB and III according to Kenney and Doig) were incubated with IL-1β (10 ng/ml) or IL-6 (10 ng/ml) for 24 h. Secretion and mRNA transcription of collagen type 1 (Col1a1) and type 3 (Col3a1), fibronectin (Fn1), Mmp-1, -2, -3, -9, -13, Timp-1, -2 were analyzed by real-time PCR and ELISA, respectively. IL-1β treatment up-regulated secretion of COL1, MMP-2, TIMP1, and TIMP2 in category I endometrial fibrosis tissues (P < 0.05). IL-6 treatment up-regulated secretion of ECM, MMP-2, and MMP-3 and down-regulated secretion of MMP-9 in category I tissues (P < 0.05). In category IIA tissues, IL-1β and IL-6 treatment up-regulated secretion of COL3 (P < 0.05; P < 0.05), and IL-6 treatment also down-regulated secretion of MMP-9 (P < 0.05). In category IIB tissues, IL-1β treatment down-regulated secretion of COL3 (P < 0.05) and up-regulated secretion of MMP-3 (P < 0.01), while IL-6 treatment up-regulated secretion of MMP-3, MMP-9, and MMP-13 (P < 0.05). In category III tissues, IL-1β treatment up-regulated secretion of COL1, MMP-1, MMP-9 and TIMP-2 (P < 0.05), and IL-6 up-regulated secretion of all investigated ECM components, MMPs and TIMPs. These results reveal that the effect of IL-1β and IL-6 on equine endometrium differs depending on the severity of endometrial fibrosis. Our findings indicate an association between inflammation and development of endometrosis through the effect of IL-1β and IL-6 on expression of ECM components, MMPs, and TIMPs in the mare.
Copyright © 2019 Elsevier Ltd. All rights reserved.
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Publication Date: 2019-06-29 PubMed ID: 31265984DOI: 10.1016/j.cyto.2019.154767Google Scholar: Lookup
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  • Research Support
  • Non-U.S. Gov't

Summary

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The study analyzes the impact of proinflammatory cytokines IL-1β and IL-6 on endometrial collagen and matrix metallopeptidase expression in horses with endometrosis, a chronic degenerative condition. The severity of the condition appears to alter the cytokines’ impact on factors involved in extracellular matrix component turnover and fibrosis.

Objective of the Research

  • The research seeks to understand how proinflammatory cytokines, specifically IL-1β and IL-6, influence the expression of collagen and matrix metallopeptidases (MMPs) in equine endometrosis. This ailment is a degenerative, chronic process that disrupts the normal functioning of a mare’s uterine endometrium.

Methodology

  • The researchers classified the severity of endometrial fibrosis into four categories: I, IIA, IIB, and III. This classification was based on the extent of degenerative changes observed in the endometrial fibrosis.
  • Endometrial explants (samples) from each category were treated with either IL-1β or IL-6 for a period of 24 hours.
  • Thereafter, the researchers analyzed the secretion and mRNA transcription of various components such as collagen type 1 (Col1a1) and type 3 (Col3a1), fibronectin (Fn1), as well as several types of Mmp and Timp.

Findings

  • Results reveal that cytokine treatment upregulates or downregulates the secretion of different components depending on the severity of endometrial fibrosis.
  • For example, IL-1β treatment increased the secretion of COL1, MMP-2, TIMP1, and TIMP2 in category I endometrial fibrosis tissues. Meanwhile, IL-6 treatment boosted the secretion of ECM, MMP-2, and MMP-3 and reduced the secretion of MMP-9 in category I tissues.
  • Moreover, in category III tissues, IL-1β treatment resulted in increased secretion of COL1, MMP-1, MMP-9 and TIMP-2, but IL-6 positively affected the secretion of all the explored ECM components, MMPs and TIMPs.

Conclusion

  • These results highlight how the impact of IL-1β and IL-6 on equine endometrium varies subject to the severity of endometrial fibrosis.
  • The study also signifies a relationship between inflammation and the development of endometrosis because of the impact of IL-1β and IL-6 on the expression of ECM components, MMPs, and TIMPs in the mare.

Cite This Article

APA
Szóstek-Mioduchowska AZ, Baclawska A, Okuda K, Skarzynski DJ. (2019). Effect of proinflammatory cytokines on endometrial collagen and metallopeptidase expression during the course of equine endometrosis. Cytokine, 123, 154767. https://doi.org/10.1016/j.cyto.2019.154767

Publication

Cytokine
ISSN: 1096-0023
NlmUniqueID: 9005353
Country: England
Language: English
Volume: 123
Pages: 154767
PII: S1043-4666(19)30196-6

Researcher Affiliations

Szóstek-Mioduchowska, A Z
  • Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland. Electronic address: a.szostek-mioduchowska@pan.olsztyn.pl.
Baclawska, A
  • Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland.
Okuda, K
  • Laboratory of Reproductive Physiology Graduate School of Environmental and Science, Okayama University, 700-8530 Okayama, Japan; Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan.
Skarzynski, D J
  • Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland.

MeSH Terms

  • Animals
  • Collagen / biosynthesis
  • Collagenases / biosynthesis
  • Endometriosis / metabolism
  • Endometriosis / pathology
  • Endometriosis / veterinary
  • Endometrium / metabolism
  • Endometrium / pathology
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Female
  • Gene Expression Regulation
  • Horse Diseases / metabolism
  • Horse Diseases / pathology
  • Horses
  • Interleukin-1beta / biosynthesis
  • Interleukin-6 / biosynthesis

Citations

This article has been cited 20 times.
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