Endometrial IL-1β, IL-6 and TNF-α, mRNA expression in mares resistant or susceptible to post-breeding endometritis

Fumuso, E.; Giguère, Steeve; Wade, J.; Rogan, D.; Videla-Dorna, Ignacio; Bowden, Robert A.

doi:10.1016/s0165-2427(03)00137-5

Cited by 96 publications

(83 citation statements)

References 26 publications

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“…These data support previous research that illustrated a local immune response in response to intrauterine challenge with dead spermatozoa (Fumuso et al 2007), and the conclusions that susceptible mares are less capable of clearing the uterine inflammation than resistant mares (Hughes & Loy 1969, Troedsson et al 1993b, Fumuso et al 2006, Woodward et al 2012. However, the results conflict with those from other studies as to which cytokines differ and at which time points (Fumuso et al 2003(Fumuso et al , 2006. A possible explanation for discrepancies between studies is the criteria by which mares are selected as resistant vs susceptible to PBIE.…”

Section: Discussionsupporting

confidence: 83%

“…Fumuso et al investigated endometrial cytokine mRNA expression 24 h after artificial insemination in susceptible and resistant mares. The group detected an increase in the pro-inflammatory cytokines interleukin-1b (IL1B), IL6, and tumor necrosis factor a (TNF (TNFA)) in all mares after insemination and found that mares susceptible to PBIE had higher basal levels of mRNA expression of the cytokines when compared with resistant mares (Fumuso et al 2003). The same group subsequently found increased mRNA expression of the neutrophil chemoattractant IL8 and lower expression of the inflammatory modulating cytokine IL10 in susceptible mares compared with resistant mares 24 h after insemination (Fumuso et al 2006(Fumuso et al , 2007.…”

Section: Introductionmentioning

confidence: 99%

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Endometrial inflammatory markers of the early immune response in mares susceptible or resistant to persistent breeding-induced endometritis

Woodward¹,

Christoffersen²,

Campos³

et al. 2013

Reproduction

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Transient endometritis after breeding is necessary for clearance of bacteria and spermatozoa; however, in a subpopulation of mares, the inflammation fails to resolve in a timely fashion. The objective of this study was to describe the uterine inflammatory response in mares susceptible or resistant to persistent breeding-induced endometritis (PBIE) during the first 24 h after induction of uterine inflammation. Twelve mares were classified as susceptible (nZ6) or resistant (nZ6) to PBIE. Mares were inseminated over five estrous cycles and endometrial biopsies were collected at one time point per cycle before (0) and 2, 6, 12, and 24 h after insemination. qPCR analysis for IL1B, IL6, IL8, IFNG, TNF (TNFA), IL10, and IL1RN was performed, and endometrial inflammatory cells were counted for each sample. Relative quantification values reported fold changes in mRNA expression from 0 h values. A general pattern of expression post insemination was observed in both groups of mares. Cytokine mRNA increased at 2 h, peaked between 2 and 12 h, and then decreased. Differences were detected between groups of mares 6 h after challenge; resistant mares had higher mRNA expression of IL6, IL1RN, and IL10 than susceptible mares. Susceptible mares had an increased number of polymorphonuclear neutrophils in the endometrium 2 and 12 h after breeding when compared with resistant mares. These findings describe an inherent difference in the initial immune response to insemination and may help explain the transient nature of inflammation in resistant mares, whereas susceptible mares develop a persistent inflammation.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Endometrial inflammatory markers of the early immune response in mares susceptible or resistant to persistent breeding-induced endometritis

Woodward¹,

Christoffersen²,

Campos³

et al. 2013

Reproduction

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“…In order to better understand equine endometritis, pro-inflammatory cytokines were studied in the endometrium from mares susceptible to endometritis (Fumuso et al 2003). This study showed no effect of the estrous cycle on mRNA expression of pro-inflammatory cytokines (interleukin: IL-1a; IL-6 and TNFa), even though mares resistant to endometritis had Fig.…”

Section: Cytokines In the Endometriummentioning

confidence: 93%

“…Specifically, during the luteal phase, the relationship between these two structures is quite evident, mainly at the time of luteolysis. Even though cytokines in the endometrium of mares were first addressed in pathologic conditions, such as endometritis (Fumuso et al 2003), lately their role on the physiologic regulation of endometrial secretory and angiogenic function has been studied (Roberto da Costa et al 2008). Specifically in the mare reproductive tract, cytokines tumor necrosis factor alpha (TNFa), interferon gamma (IFNg), Fas ligand (FASL), transforming growth factor beta (TGFa), and interleukins (IL) have been related to luteal secretory capacity (Galvão et al 2010); endometrial and/or trophoblast growth and differentiation during placentation (Lennard et al 1995) and endometrial response to semen (Palm et al 2008).…”

Section: Cytokines In the Endometriummentioning

confidence: 99%

Cytokines and neutrophil extracellular traps in the equine endometrium: friends or foes?

Galvão¹,

Rebordão²,

Szóstek³

et al. 2012

PHK

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SummaryCytokines may play a dual role in the reproductive tract -either involved in physiologic processes or mediating inflammation and other pathologic processes. Physiologic secretory and angiogenic function in the equine endometrium appears to be regulated by cytokines TNFa, FasL, IFNg through their receptors. These receptors are present in glandular epithelium, and stroma cells and their mRNA expression changes throughout the estrous cycle. Besides, interleukins (IL-1a and IL-1b) and their receptors mRNA expression vary according to various degrees of endometrium inflammation (endometritis) and fibrosis (endometrosis). A novel paradigm in innate immunity and neutrophils (PMN) hyperactivation is PMN ability to cast out their DNA in response to infectious stimuli. These PMN extracellular traps (NETs) bind and kill pathogens, at the infection site. The intriguing dilemma is that even though NETs may function as a first line of defense, they also release molecules that may contribute to tissue damage. Thus, we postulate that PMN present in the endometrium at estrus, mating or infection, might form NETs, and release nucleic and cytoplasmic proteins with immunomodulatory properties. Equine PMN stimulated in vitro showed NETs formation capacity when in contact with some bacteria strains obtained from mares with endometritis, such as Streptococcus zooepidemicus, Escherichia coli and Staphylococus capitis. In this regard, even though NETs and cytokines function as an effective antimicrobial first line of defense or modulate physiologic endometrial function, respectively (friends), they may also be involved in endometrial fibrosis pathogenesis and endometrial secretory function impairment, due to enhanced NETs formation and/or a decrease on NETs degradation (foes).Keywords: Neutrophil extracellular traps; cytokines, mare, endometrium, endometritis, reproductionZytokine und "neutrophile extrazelluläre Fallen" im Endometrium des Pferdes -Freund oder Feind?Zytokine können im Reproduktionstrakt in zweifacher Hinsicht eine Rolle spielen: zum einen sind sie an physiologischen Prozessen beteiligt, zum anderen vermitteln sie bei Entzündungen oder anderen Alterationen. Die equine endometriale physiologische sekretorische und angiogene Funktion scheint durch die Zytokine TNFa, FasL, IFNg durch ihre Rezeptoren reguliert zu werden. Diese sind in den glandulären Epithelien und den Stromazellen lokalisiert, ihre mRNA Expression ist innerhalb des Zyklusgeschehens veränderlich. Darüber hinaus variieren die Interleukine (IL-1a und IL-1b) und ihre Rezeptor-mRNA-Expression in Abhängigkeit vom Grad der Endometritis und Endometrose (periglanduläre Fibrose). Ein neues Denkmodell bezüglich der angeborenen Immunität und der Hyperaktivität der neutrophilen Granulozyten (PMN) ist die Ausschüttung ihrer DNA als Reaktion auf einen infektiösen Stimulus. Diese neutrophil extracelluar traps -"Neutrophile extrazelluläre Fallen", NETs, binden und töten pathogene Keime, im Falle einer Infektion. Das faszinierende Dilemma dabei ist, dass obwohl NETs ih...

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“…Recently, Fumuso et al [12,13] reported that mares susceptible to developing persistent endometritis have higher endometrial expression of proinflammatory cytokines and lower levels of the anti-inflammatory cytokines. In addition, Watson et al [30] reported that mares with elevated plasma concentrations of P 4 had decreased bactericidal activity of neutrophils in the uterus.…”

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confidence: 99%

Effect of Progesterone on the <i>in vitro</i> Response of Peripheral Blood Mononuclear Cells Stimulated by <i>Escherichia coli</i> in Mares

Maeda

Ohtsuka

Tomioka

et al. 2012

The Journal of Veterinary Medical Science

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ABSTRAcT. Escherichia coli(E. coli) isolated from the uterus of a Thoroughbred mare with bacterial endometritis was used to evaluate the effect of progesterone (P 4 ) on the immune response of mares. Peripheral blood mononuclear cells (PBMcs) were collected from 10 nonpregnant clinically healthy adult mares (range, 4-12 years) during diestrus, four Thoroughbreds and six Hokkaido native horses. Cell proliferation and expression of cytokine mRNA, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-10, of PBMcs stimulated with E. coli and P 4 were examined in vitro. P 4 was shown to have significantly inhibited E. coli induced proliferation and expression of IFN-γ in PBMCs. These results indicate that P 4 inhibits the immune response to E. coli in mares. KEY WORDS: bacterial endometritis, cytokine, Escherichia coli, mare, progesterone.doi: 10.1292/jvms.11-0364; J. Vet. Med. Sci. 74(5): 629-632, 2012 Endometritis is the third most common medical condition in horses [28] that causes infertility and results in major losses in the equine breeding industry. To date, bacterial uterine infection has been reported to occur in 25-60% of barren mares [2,5,7] and Escherichia coli(E. coli) are most frequently associated with fertility problems in mares [1]. It was reported that the endometrium of the mare shows an enhanced ability to eliminate infection during the follicular phase compared with the luteal phase of the estrous cycle [14]. Previous studies suggest that progesterone (P 4 ) is closely associated with the incidence of bacterial endometritis and that P 4 dominated uterus exhibits reduced physical clearance of bacteria in the mare [10]. These findings suggest that P 4 significantly affects the incidence of endometritis.Inflammation is initiated and maintained by the emergence of a network of proinflammatory cytokines, such as interferon (IFN)-γ and tumor necrosis factor (TNF)-α, and anti-inflammatory cytokines, such as interleukin (IL)-10 [24]. Recently, Fumuso et al. [12,13] reported that mares susceptible to developing persistent endometritis have higher endometrial expression of proinflammatory cytokines and lower levels of the anti-inflammatory cytokines. In addition, Watson et al. [30] reported that mares with elevated plasma concentrations of P 4 had decreased bactericidal activity of neutrophils in the uterus. Also, in anestrus dogs, P 4 caused significant inhibition of the proliferation of peripheral blood mononuclear cells (PBMcs) in response to E. coli isolated from the uterus affected by pyometra [27]. Progesterone inhibits the proliferation of peripheral blood lymphocytes activated by mitogens in humans [22], cows [3], sheep [16] and pigs [31]. Progesterone treatment of mares has been associated with prolonged infection after intrauterine inoculation with bacteria [4,14]. These reports in different species indicate that not only the status of systemic immunity affected by P 4 was associated with bacterial growth in the uterus but also that the immunosuppressive effects of P...

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Endometrial IL-1β, IL-6 and TNF-α, mRNA expression in mares resistant or susceptible to post-breeding endometritis

Cited by 96 publications

References 26 publications

Endometrial inflammatory markers of the early immune response in mares susceptible or resistant to persistent breeding-induced endometritis

Endometrial inflammatory markers of the early immune response in mares susceptible or resistant to persistent breeding-induced endometritis

Cytokines and neutrophil extracellular traps in the equine endometrium: friends or foes?

Effect of Progesterone on the <i>in vitro</i> Response of Peripheral Blood Mononuclear Cells Stimulated by <i>Escherichia coli</i> in Mares

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