INTRODUCTION
In dairy cattle, efficient milk production continues to require for pregnancy and parturition each year. During pregnancy and parturition, maternal immune responses are suppressed to contribute to fetal survival, which is also known as maternal tolerance of the fetus [1, 2]. In general, Th1/Th2 imbalance and regulatory T cell (Treg) induction are known to be involved in maternal tolerance [3, 4]. Sex hormones, such as estradiol and progesterone, play important roles in the inhibition of Th1 responses and induction of Tregs [5, 6]. Previous report has shown that sex hormones contribute to the suppression of immune responses in pregnant cattle [7]. Although immune suppression in pregnant animals is essential for the prevention of fetal injury by the maternal immune system, this suppression may affect the progression and onset of bovine chronic diseases, such as bovine leukosis. Bovine leukemia virus (BLV) is a member of the genusDeltaretrovirus , and causes bovine leukosis after a long latent period [8]. Most BLV-infected cattle remain subclinical and are referred to as aleukemic. However, approximately 30% of BLV-infected cattle develop persistent lymphocytosis, which is characterized by the nonmalignant polyclonal expansion of infected B cells in peripheral blood. Less than 5% of BLV-infected cattle develop bovine leukosis, which is called enzootic bovine leukosis (EBL) and is characterized by fatal lymphoma or lymphosarcoma [9]. The suppression of the immune system, particularly in a stressful situation such as parturition, is considered a risk factor for the development of bovine leukosis [10, 11]. Although parturition is an important event for progression to the clinical stages of BLV infection, the relationship between parturition and the progression of these diseases has not been fully elucidated.
Prostaglandin E2 (PGE2) is an inflammatory mediator that is metabolically derived from arachidonic acid by cyclooxygenase enzymes (COX-1 and COX-2) [12]. COX-1 is a constitutive enzyme that is expressed in many tissues including the kidneys, stomach, and vascular endothelium, and it is involved in a multitude of physiological processes [13]. Conversely, COX-2 is an inducible enzyme that is regulated by inflammatory cytokines, antigen-stimulation, and growth factors via the activation of nuclear factor-kappa B (NF-κB) [14]. PGE2 inhibits the activities of immune cells such as T cells, dendritic cells, and natural killer cells via prostaglandin E receptor (EP) 2 and EP4, thereby contributing to immune evasion during chronic infections [15]. Our previous studies have demonstrated that PGE2 inhibits Th1 responses in cattle, and is associated with the progression of BLV infection [16, 17]. In addition, PGE2, as well as PGF, is an important factor related to the induction of parturition in cattle [18]. However, little information is available regarding the immune dysfunctional effect of PGE2 in periparturient period. Therefore, to investigate whether PGE2 is involved in the suppression of immune responses in the periparturient period, PGE2 kinetics and Th1 cytokine production were analyzed in the present study by using BLV-infected pregnant cattle.