Effects of Prostaglandin F2α and Progesterone on the Ability of Bovine Luteal Cells to Stimulate T Lymphocyte Proliferation1

Cannon, Matthew; Petroff, Margaret G.; Pate, Joy L.

doi:10.1095/biolreprod.103.017590

Cited by 28 publications

(27 citation statements)

References 34 publications

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“…Although a synthetic antagonist of P4 (onapristone) has been shown to be specific for intracellular P4 receptors [28], P4 seems to act on the secretory function of bovine CL [36] and endometrium nongenomically [37] (i.e., through membrane binding sites [32], rather than through nuclear mediation). In support of this idea, Cannon et al [38] has recently shown that P4 suppresses luteal cells-stimulated T lymphocyte proliferation. However, classical-genomic P4 receptors were not expressed in T lymphocytes, showing that P4 may act nongenomically on the cells [38].…”

Section: Discussionmentioning

confidence: 87%

Progesterone Is a Suppressor of Apoptosis in Bovine Luteal Cells1

Okuda

Korzekwa

Shibaya

et al. 2004

Biology of Reproduction

114

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Progesterone is suggested to be a suppressor of apoptosis in bovine luteal cells. Fas antigen (Fas) is a cell surface receptor that triggers apoptosis in sensitive cells. Furthermore, apoptosis is known to be controlled by the bcl-2 gene/protein family and caspases. This study was undertaken to determine whether intraluteal progesterone (P4) is involved in Fas L-mediated luteal cell death in the bovine corpus luteum (CL) in vitro. Moreover, we studied whether an antagonist of P4 influences gene expression of the bcl-2 family and caspase-3 and the activity of caspase-3 in the bovine CL. Luteal cells obtained from the cows in the midluteal phase of the estrous cycle (Days 8-12 of the cycle) were exposed to a specific P4 antagonist (onapristone [OP], 10(-4) M) with or without 100 ng/ml Fas L. Although Fas L alone did not show a cytotoxic effect, treatment of the cells with OP alone or in combination with Fas L resulted in killing of 30% and 45% of the cells, respectively (P <0.05). DNA fragmentation was observed in the cells treated with Fas L in the presence of OP. The inhibition of P4 action by OP increased the expression of Fas mRNA (P <0.01); however, it did not affect bax or bcl-2 mRNA expression (P >0.05). Moreover, OP stimulated expression of caspase-3 mRNA (P <0.01). The overall results indirectly show that intraluteal P4 suppresses apoptosis in bovine luteal cells through the inhibition of Fas and caspase-3 mRNA expression and inhibition of caspase-3 activation.

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Section: Discussionmentioning

confidence: 87%

Progesterone Is a Suppressor of Apoptosis in Bovine Luteal Cells1

Okuda

Korzekwa

Shibaya

et al. 2004

Biology of Reproduction

114

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“…Also, P 4 treatment of mares has been associated with prolonged infection after intrauterine inoculation with bacteria [4,14]. Thus, the immunosuppressive effects of P 4 are well known in different species [3,4,16,22,31]. Our results show reduced cell proliferation and suggests that antigen-specific lymphocyte activity is downregulated by P 4 , and this effect might allow the development of bacterial infections in the presence of P 4 .…”

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confidence: 65%

“…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].…”

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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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“…However, it is still unclear whether or not P 4 had no effective to immune response in the low BCS cows. P 4 containing medicines are frequently administered in treatment of repeat-breeding cows because high milk yield dairy cows have low progesterone levels during the luteal phase; however the immunosuppressive effect of this steroid hormone should be considered when determining the appropriate treatment [1]. Further studies are needed to clarify the mechanism of the effect of P 4 on lymphocyte function in dairy cows in order to maintain their health and prevent mastitis.…”

Section: Resultsmentioning

confidence: 99%

Effect of Body Condition Score of the Dairy Cow on the in vitro Immune Response of Peripheral Blood Mononuclear Cells to Progesterone Stimulation

Ohtsuka

Murase

Ando

et al. 2009

The Journal of Veterinary Medical Science

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ABSTRACT. Immune function in cows is closely associated with their physical and hormonal conditions. In order to clarify the relationship between the body condition score (BCS) of lactating dairy cows and the immune response to progesterone (P 4 ) in vitro, we examined whether lower BCS in dairy cows affects the responsiveness of peripheral blood mononuclear cells (PBMCs) to P 4 added in to culture medium. Forty-two non-pregnant healthy Holstein dairy cows were examined at 61 to 120 days after calving. The cows were divided into the following two groups; Low BCS group (N=20), which had a BCS of less than 2.25, and a Control group (N=22), which had a BCS over 2.75. PBMCs were stimulated with P 4 (1 g/mL) and/or phytohemagglutinin (PHA), and the levels of cytokine mRNA were analyzed. In the Low BCS group, a significantly lower IFN- level was stimulated by PHA only compared with the Control group. The combination of P 4 and PHA significant decreased the IFN-/IL-4 ratio in the Control group, but this reaction was not found in the Low BCS group. Our data indicated that expression of IFN- mRNA was basically lower in the low BCS dairy cows and that addition of P 4 did not suppress the cellular immune function in these cows. In this study, we observed that P 4 reduced the cellular immune response in the adequate BCS cows, whereas immunosuppression by P 4 was not found in the PBMCs of the low BCS cows, which already had a lower level of immune function. KEY WORDS: body condition score, dairy cow, immune function, progesterone.J. Vet. Med. Sci. 71 (5): [549][550][551][552][553] 2009 Mastitis and endometritis are frequently observed in dairy cows, and these diseases affect productivity. Yield and quality of milk decrease in mastitic cows, and reproductive performance declines in cows with endometritis. Deluyker et al. [4] reported that occurrence of clinical mastitis is associated with 5% milk yield loss and that cows with a mean SCC greater than 245,000 cells/ml over 119 d show a 6.2% yield loss compared with cows with an SCC of 90,000 cells/ ml or less. Failure of immune function to prevent bacterial invasion in the mammary gland or uterus is closely related to the occurrence of these infectious diseases [11]. Low body condition score (BCS) is closely associated with morbidity in the dairy cow [6,20], and a higher somatic cell count (SCC) or clinical mastitis is frequently observed in low BCS cows [21].It is well known that cows with a BCS of less than 2.25 have reduced breeding performance [5,15]. Progesterone (P 4 ) is important for fertility as demonstrated by the positive correlation between the serum P 4 level at the time of artificial insemination and the subsequent conception rate. Therefore, P 4 supplementation is used frequently to improve the serum P 4 level in order to enhance the reproductive performance of dairy cows with low serum P 4 levels, such as lower BCS cows [18]. On the other hand, P 4 is well known as one of the hormones that suppresses immune function. Previous studies in the mouse have re...

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Effects of Prostaglandin F2α and Progesterone on the Ability of Bovine Luteal Cells to Stimulate T Lymphocyte Proliferation1

Cited by 28 publications

References 34 publications

Progesterone Is a Suppressor of Apoptosis in Bovine Luteal Cells1

Progesterone Is a Suppressor of Apoptosis in Bovine Luteal Cells1

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

Effect of Body Condition Score of the Dairy Cow on the in vitro Immune Response of Peripheral Blood Mononuclear Cells to Progesterone Stimulation

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