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
PGF2α, 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.