Ovarian steroid-dependent tumor necrosis factor-α production and its action on the equine endometrium in vitro

Szóstek, A.Z.; Adamowski, Marek; Galvão, António; Ferreira‐Dias, Graça; Skarzynski, Dariusz J.

doi:10.1016/j.cyto.2014.02.005

Cited by 18 publications

(8 citation statements)

References 30 publications

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“…Nevertheless, the present study confirmed expression of TNF-α protein in the endometrial superficial and glandular epithelium, as well as in stromal cells. This is in agreement with the study of Szóstek and coworkers [ 18 ], in which the direct production of TNF-α by in vitro cultured equine endometrial epithelial and stromal cells was shown by the ELISpot method or by IHC [ 33 ].…”

Section: Discussionsupporting

confidence: 93%

“…In fact, TLR4 was shown to mediate a lipopolysaccharide (LPS)-challenge response in murine [ 14 ] as well as in bovine [ 16 ] epithelial and stromal endometrial cells. Moreover, the production and secretion of a pleiotrophic cytokine, TNF-α, was confirmed in cultured feline [ 17 ] and equine [ 18 ] endometrial cells. The severity of inflammation seems to be dependent on several factors, including bacterial strain, innate immunity and general condition of the female.…”

Section: Introductionmentioning

confidence: 99%

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Type of Inflammation Differentially Affects Expression of Interleukin 1β and 6, Tumor Necrosis Factor-α and Toll-Like Receptors in Subclinical Endometritis in Mares

Siemieniuch

Szóstek

Gajos³

et al. 2016

PLoS ONE

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Mares that fail to conceive or lose their embryos, without showing typical signs of clinical endometritis, should be suspected of subclinical endometritis (SE). In this study, the question was addressed: does SE fully activate selected mechanisms of innate immunity in mares? For this aim, expression of mRNAs for Toll-like Receptor 2 and 4 (TLR 2/4), interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor α (TNF) was examined in control mares versus either mares suffering from chronic endometritis (ChE) or subacute suppurative endometritis (SSE). The concentrations of IL-1β, IL-6 and TNF-α in supernatants from endometrial tissue cultures after 4 h incubation were measured using the enzyme immunoassay (EIA) method. Eighty-two warmblood mares, of known breeding history, were enrolled in this study. Based on histopathological assessment, mares were classified as suffering from ChE, SSE or as being healthy. In addition, immuno-localization of both TLR2 and TLR4 as well as TNF-α was investigated in the equine endometria. The mRNA expression of TLR2 (P < 0.01), IL-1β (P < 0.0001), IL-6 (P < 0.0001) and TLR4 and TNF (P < 0.05) was up-regulated in endometria of mares suffering from SSE compared with unaffected mares. Concentrations of IL-6 and TNF-α were increased only in mares exhibiting SSE, compared with unaffected (P < 0.01 for both) and ChE mares (P < 0.05 for both). Immuno-localization of TNF-α and TLRs was confirmed, both in unaffected and SE-affected endometria, and was present in the luminal and glandular epithelia and stromal cells. The severity of inflammation impacts the immune response and fosters activation of innate immunity mechanisms, as observed in the endometria of mares. The intracellular localization of TLRs and TNF-α in the endometria indicates a key role of endometrial epithelial and stromal cells in the immune response and inflammation.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Type of Inflammation Differentially Affects Expression of Interleukin 1β and 6, Tumor Necrosis Factor-α and Toll-Like Receptors in Subclinical Endometritis in Mares

Siemieniuch

Szóstek

Gajos³

et al. 2016

PLoS ONE

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“…The cytokine TNFA is considered to be indicative of acute inflammatory process but it is also involved in the regulation of equine estrus cycle [31, 32]. In their study, Centeno et al [31] found any differences in TNFA expression in endometrial tissue of mares with different degree of fibrosis; the expression of TNFA in our study was greater in G1 mares than older ones.…”

Section: Discussioncontrasting

confidence: 44%

Different expression of Defensin-B gene in the endometrium of mares of different age during the breeding season

et al. 2019

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BackgroundDespite being one of the major causes of infertility in mares, the mechanisms responsible for equine endometrosis are still unclear and controversial. In the last few years, many investigations focused on local immune response modulation. Since it is generally accepted that endometrial fibrosis increases with age, we hypothesize that older mares could show altered local immune modulation, initiating a pro-inflammatory and tissue remodeling cascade of events that could lead to endometrosis. The aim of this study, indeed, is to evaluate and describe the local gene expression of genes involved in acute inflammatory response and fibrosis (COL1A1, COL3A1, TNFA, MMP9, IL6, TGFB1 and TGFBR1), together with others associated to immune modulation (DEFB4B, IDO1 and FOXP3), in uterine specimens from mares of different age.ResultsTwenty-five Standardbred mares were involved in the study with age ranging from 7 to 19 years (mean 10.40 ± 4.42). They were divided by age into two groups: G1 (n = 15, less than 10 years old) and G2 (N = 10, greater than 11 years old). Specimens from the uterus’ right horn-body junction were collected and processed for histology evaluation and RT-qPCR assay.Gene expression of DEFB4B, MMP9 and TNFA was higher in younger mares, suggesting a balance in immune modulation and tissue remodeling. Interleukin-6 and COL3A1 gene expressions were greater in older animals, probably indicating inflammatory pathways activation and fibrosis increase. Although no differences in fibrosis and inflammation distribution could be found with histological examination among G1 and G2, our results suggest a possible involvement of DEF4BB in regulating the local immune response in younger mare’s uterus (G1); age may contribute to the dis-regulation of DEFB4B transcription and, indirectly, influence the extracellular matrix homeostasis. Transcription of IDO1 and FOXP3 genes, instead, does not seem to be age related, or to be involved in local immune-response and tissue remodeling functions.ConclusionsFurther investigations are needed in order to clarify the interactions between the expression of DEFB4B, IL6, TNFA, COL3A1 and MMP9 and other local signals of immune-modulation and tissue remodeling, in mares in a prospective study design.

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“…Since TNF- is one of Th1 cytokines, the result of the present study seems to be unreasonable. However, it is reported that TNF- can increase the protein content of PGG/H synthase, PGF synthase and PGE synthase in cultured bovine oviductal epithelial cells (Szóstek et al, 2011), and TNF- stimulates PGE2 production to a large extent and PGF2 secretion to a lesser extent in equine endometrial explants (Szóstek et al, 2014). PGE2 is a luteotrophic factor, while PGF2 is a luteolytic factor.…”

Section: Resultsmentioning

confidence: 99%

Changes in expression of Th1 and Th2 cytokines in bovine peripheral blood mononuclear cells during early pregnancy

Yang¹,

Wang²,

Xingshu³

et al. 2015

IJAR

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Conceptus-derived signals are involved in the maternal systemic immune regulation through blood circulation and lymph circulation by peripheral blood mononuclear cells (PBMC) in cattle. There exists a Th2-biased response in maternal uterus during early pregnancy in cattle. However, it is unclear that the changes in expression of Th1 and Th2 cytokines in PBMC during early pregnancy in cows. At present study, the expression of Th1 and Th2 cytokines in PBMC were explored at day 18 non-pregnant cows, day 18 and day 30 pregnant cows. Our results showed that IFN- was attenuated in PBMC, but TNF- and IL-2 in PBMC were up-regulated during early pregnancy in cows. However, the member of the Th2 cytokines, including IL-4, IL-5, IL-6, IL-10 and IL-13, was augmented in day 30 pregnant PBMC. In conclusion, there existed a Th2-biased response in PBMC during early pregnancy, which was essential for successful pregnancy in cattle.

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Ovarian steroid-dependent tumor necrosis factor-α production and its action on the equine endometrium in vitro

Cited by 18 publications

References 30 publications

Type of Inflammation Differentially Affects Expression of Interleukin 1β and 6, Tumor Necrosis Factor-α and Toll-Like Receptors in Subclinical Endometritis in Mares

Type of Inflammation Differentially Affects Expression of Interleukin 1β and 6, Tumor Necrosis Factor-α and Toll-Like Receptors in Subclinical Endometritis in Mares

Different expression of Defensin-B gene in the endometrium of mares of different age during the breeding season

Changes in expression of Th1 and Th2 cytokines in bovine peripheral blood mononuclear cells during early pregnancy

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