Interleukin-4 -590 (C>T), toll-like receptor-2 +2258 (G>A) and matrix metalloproteinase-9 -1562 (C>T) polymorphisms in pre-eclampsia.

Functional single nucleotide polymorphisms (SNPs) of interleukin (IL)-4 -590 (C>T), toll-like receptor (TLR)-2 +2258 (G>A) and matrix metalloproteinase (MMP)-9 -1562 (C>T) were examined by polymerase chain reaction-restriction fragment length polymorphism to identify their merit as genetic markers for pre-eclampsia. One hundred and seventeen pre-eclamptic women and 146 control subjects with uncomplicated singleton pregnancies participated in this study, conducted at Leeds General Infirmary and St James's University Hospital. While the TLR-2 +2258 (G>A) and MMP-9 -1562 (C>T) SNPs failed to present any significant association with pre-eclampsia, there was a marked trend for an association between the IL-4 -590 (C>T) SNP and pre-eclampsia (chi(2)= 5.87, P = 0.055), with a prevalence of TT homozygous women in this group (OR 4.455, 95% CI 1.286-15.350).

Host inflammatory response profiling in preeclampsia using an in vitro whole blood stimulation model.

The pathophysiology of preeclampsia (PET) implicates an inflammatory dysfunction. This study profiled this host response by challenging whole blood with lipopolysaccharide. Multiplex immunoassays determined interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p70), IL-13, IL-17, granulocyte/granulocyte macrophage-colony stimulating factors (G-CSF/GM-SCF), interferon(IFN)-gamma, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein-1beta and tumor necrosis factor (TNF)-alpha levels. Secretory capacity was expressed in pg/million white cells or monocytes (+/-SEM). PET featured significantly higher IL-1beta, IL-2, IL-10, IL-13, G-CSF, IFN-gamma, MCP-1 and TNF-alpha monocyte secretory capacities (p < 0.05). The PET group exhibited an inflammatory hyper-responsiveness (p < 0.01) which was poorly described by the traditional Th1:Th2 dichotomy.

Murine serum cytokines throughout the estrous cycle, pregnancy and post partum period.

Cytokines are pleiotropic glycoproteins participating in many aspects of mammalian reproductive physiology. Although murine models have been established to study normal and pathological pregnancy, the small volume of retrievable sample has hampered investigations into the role of cytokines in these processes. These problems were overcome by using fluid-phase multiplex immunoassays to monitor the serum profiles of 18 cytokines in single animals throughout normal murine reproduction: estrus, diestrus, post coitum, preimplantation, implantation, mid-pregnancy, late pregnancy and post partum. Most cytokines were detectable throughout all stages studied. Modest changes in profile were associated with estrous cyclicity and early pregnancy while virtually all cytokine levels increased markedly in mid- to late pregnancy and either fell slightly or levelled off post partum. The functional interrelationships between the various cytokines and the hormonal milieu are discussed with respect to gestational stage. Although certain profiles supported the 'conventional' Th1:Th2 cytokine paradigm of pregnancy, many of the changes recorded were orchestrated around IL-12 (p40) and (p70). The present findings suggest that the traditional cytokine dichotomy poorly describes complex immunological processes like pregnancy.

Angiotensin I-converting enzyme (ACE) activity of the tomato moth, Lacanobia oleracea: changes in levels of activity during development and after copulation suggest roles during metamorphosis and reproduction.

Angiotensin I-converting enzyme (ACE) is a dipeptidyl carboxypeptidase that removes C-terminal dipeptides from relatively short oligopeptides, usually smaller than 15 amino acids. In mammals, the enzyme has several important roles in the metabolism of vasoactive peptides, but its physiological role in insects is not fully understood. We now report the properties of an ACE in a lepidopteran species (the tomato moth, Lacanobia oleracea) and suggest new physiological roles for the enzyme in this insect. ACE activity increases four-fold during the last stadium and in early pupae, a rise which, in its timing, is similar to what has been observed previously in the transition of larva to pupa in Drosophila melanogaster. This suggests that the increase in ACE activity might be of general importance for peptide metabolism during metamorphosis in holometabolous insects. High levels of ACE activity were found in the haemolymph of sixth stadium larvae and adult insects, and in the reproductive tissues of both male and female adults. Almost all of the ACE activity in the reproductive tissues was found in the accessory glands of the male and the spermatheca and bursa copulatrix of the female. The decline in accessory gland ACE in mated males and the concomitant rise in ACE activity in the spermatheca and bursa copulatrix of the female suggested the transfer of ACE from the male to the female during copulation. Using several convenient peptides as substrates, we have shown that the spermatophore/bursa copulatrix taken from mated female insects possess an aminopeptidase, a carboxypeptidase and a dipeptidase, in addition to high levels of ACE. These peptidases might be involved in the breakdown of proteins to peptides and eventually to amino acids in the spermatophore. Evidence for such a proteolytic pathway and its role in providing substrates for the TCA cycle has been obtained previously in a study of reproduction in Bombyx mori.

A mosquito (Anopheles stephensi) angiotensin I-converting enzyme (ACE) is induced by a blood meal and accumulates in the developing ovary.

Angiotensin I-converting enzyme (ACE) has a key role in regulating levels of several circulating peptides in mammals and has a vital role in male fertility. ACE has recently been found in insects, where its role is unclear. A mutant allele of the ACE gene (Ance) of Drosophila melanogaster is embryonic lethal, indicating an important role for the enzyme in development. We now report the presence of ACE in female Anopheles stephensi mosquitoes and that the enzyme is induced by a blood meal. ACE accumulates in developing ovaries and passes into the mosquito eggs, where it may play a role in the metabolism of peptides during embryogenesis. The ovarian ACE has an Mr of 70 kDa and is inhibited by captopril and lisinopril with IC50 values of 0.1 microM and 0.6 microM, respectively.

Insect angiotensin-converting enzyme. A processing enzyme with broad substrate specificity and a role in reproduction.

Insect angiotensin-converting enzyme (ACE) is a peptidyl dipeptidase that removes dipeptides and dipeptideamides from the C-terminus of a broad range of in vitro oligopeptide substrates. In mammals, ACE has important roles in blood homeostasis and a recently recognized, but as yet undefined, role in the fertility of male mice. High levels of ACE are found in the male reproductive tissues of several insect species, and emerging data indicates an important role for the enzyme in insect reproduction. In this paper we review some of the recent findings about insect ACE, and we speculate as to the physiological role of this enzyme in insect reproduction.