Labour-associated increase in interleukin-1 α release in vitro by human gestational tissues

1996 ◽  
Vol 150 (3) ◽  
pp. 515-522 ◽  
Author(s):  
N Laham ◽  
S P Brennecke ◽  
K Bendtzen ◽  
G E Rice
Keyword(s):  
Amniotic Fluid ◽  
Time Course ◽  
Interleukin 1 ◽  
Maternal Plasma ◽  
Bacterial Endotoxin ◽  
Tissue Explants ◽  
Gestational Tissues ◽  
Term Labour ◽  
Labour Onset

Abstract The aims of this study were to investigate the concentration and release of interleukin-1α (IL-1α) at the time of human term labour, and to study the regulation of IL-1α release from human gestational tissue explants by bacterial endotoxin. Immunoreactive IL-1α concentrations in maternal plasma, amniotic fluid and conditioned media from human amniotic, choriodecidual and placental explants were quantified before and after spontaneous term labour-onset and delivery. Furthermore, the effects of a bacterial endotoxin, lipopolysaccharide (LPS), on the release of IL-1α from human gestational tissue explants over a time course of 24 h (n=3) and LPS concentrations ranging from 10–107 pg/ml (n=3) were investigated. IL-1α concentrations in maternal plasma and amniotic fluid did not change significantly with spontaneous term labour-onset. In contrast, IL-1α was released in detectable amounts from human amniotic and choriodecidual explants only in association with term labour-onset and delivery. Similarly, placental release of IL-1α was increased significantly in explant cultures in association with term labour-onset and delivery. LPS increased IL-1α release significantly only from human placental explants from both term not-in-labour and term after-labour tissues. The data demonstrate differential regulation of IL-1α release from human gestational tissues in association with labour and LPS treatment and the observations support the hypothesis that the labour-associated increase in IL-1α release from the fetal membranes is independent of exposure to bacterial endotoxin. Journal of Endocrinology (1996) 150, 515–522

Differential release of interleukin-6 from human gestational tissues in association with labour and in vitro endotoxin treatment

1996 ◽  
Vol 149 (3) ◽  
pp. 431-439 ◽  
Author(s):  
N Laham ◽  
S P Brennecke ◽  
K Bendtzen ◽  
G E Rice
Keyword(s):  
Amniotic Fluid ◽  
Interleukin 6 ◽  
Elective Caesarean Section ◽  
Fold Increase ◽  
Dependent Manner ◽  
Explant Cultures ◽  
Gestational Tissues ◽  
Term Labour ◽  
Labour Onset

Abstract In this study, we quantified interleukin-6 (IL-6) concentrations in amniotic fluid at term and preterm labour, and determined the gestational tissue source of IL-6. In addition, aspects of the regulatory mechanisms involved in IL-6 release at the time of term labour and in response to bacterial endotoxin, lipopolysaccharide (LPS), have been established. IL-6 concentrations were 2-fold higher in amniotic fluid collected at term compared with preterm gestation, with an additional 2-fold increase in association with term labour. IL-6 was released from all choriodecidual and placental explants but was detected in only 33% of amniotic explant cultures of tissues obtained before labour onset. In contrast, IL-6 was detected in all amniotic, choriodecidual and placental cultures of tissues obtained after term labour onset and delivery, and the mean IL-6 release was significantly higher than that measured in explant cultures of both amniotic (80-fold increase, P<0·0001) and choriodecidual (3-fold increase, P<0·02) but not placental explants taken at the time of elective Caesarean section at term before labour onset. LPS significantly (P<0·05) increased the release of IL-6 from human choriodecidual and placental explants but not amniotic explants, in a time- and dose-dependent manner. IL-6 is a physiological constituent of amniotic fluid and its production by gestational tissues is differentially regulated by LPS and spontaneous labour onset and delivery. Journal of Endocrinology (1996) 149, 431–439

Pattern differences in experimental fevers induced by endotoxin, endogenous pyrogen, and prostaglandins

1988 ◽  
Vol 254 (4) ◽  
pp. R633-R640 ◽  
Author(s):  
A. Morimoto ◽  
T. Nakamori ◽  
T. Watanabe ◽  
T. Ono ◽  
N. Murakami
Keyword(s):  
Time Course ◽  
Interleukin 1 ◽  
Bacterial Endotoxin ◽  
Endogenous Pyrogen ◽  
Prolonged Time ◽  
Fever Onset ◽  
Long Latency ◽  
Low Concentrations ◽  
High Concentrations ◽  
Experimentally Induced

To distinguish pattern differences in experimentally induced fevers, we investigated febrile responses induced by intravenous (IV), intracerebroventricular (ICV), and intra-preoptic/anterior hypothalamic (POA) administration of bacterial endotoxin (lipopolysaccharide, LPS), endogenous pyrogen (EP), human recombinant interleukin-1 alpha (IL-1), and prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Intravenous LPS, EP, or IL-1 in high concentrations caused biphasic fever. In low concentrations, they induced only the first phase of fever. Latency to onset and time to first peak of fever induced by IV injection of LPS or EP were almost the same as those after ICV or POA injection of PGE2. Fever induced by ICV or POA administration of LPS, EP, IL-1, or PGF2 alpha had a long latency to onset and a prolonged time course. There were significant differences among the latencies to fever onset exhibited by groups that received ICV or POA injections of LPS, EP, or PGF2 alpha and by groups given IV injections of LPS or EP and ICV or POA injections of PGE2. Present observations indicate different patterns of fever produced by several kinds of pyrogens when given by various routes. These results permit us to consider the possibility that there are several mediators or multiprocesses underlying the pathogenesis of fever.

scholarly journals Localisation and temporal changes in prostaglandin G/H synthase-1 and -2 content in ovine intrauterine tissues in relation to glucocorticoid-induced and spontaneous labour

2000 ◽  
Vol 165 (2) ◽  
pp. 399-410 ◽  
Author(s):  
WJ McLaren ◽  
IR Young ◽  
GE Rice
Keyword(s):  
Time Course ◽  
Polyclonal Antibodies ◽  
Placental Tissue ◽  
Fold Increase ◽  
Fetal Membranes ◽  
Western Blots ◽  
Protein Levels ◽  
Tissue Extracts ◽  
Term Labour ◽  
Labour Onset

Parturition in the ewe is preceded by an increase in the synthesis of prostaglandins (PGs) by gestational tissues. To establish the uterine source of these PGs, placental cotyledons, fetal membranes and maternal uterine tissues were collected from ewes (n=6) at spontaneous parturition. Solubilised tissue extracts were prepared and analysed by Western blots using polyclonal antibodies to PG G/H synthase-1 and -2 (PGHS-1 and PGHS-2). PGHS-1 was expressed by all intrauterine tissues at term labour. Densitometric analysis of Western blot autoradiographs showed that the fetal membranes and maternal cervix contained the largest amounts of PGHS-1. PGHS-1 enzyme content of ovine amnion was significantly greater than that of either chorion or allantois (P<0.05). PGHS-1 protein content of myometrial, endometrial and cotyledonary tissue extracts was minimal. Formation of the PGHS-2 isozyme was confined to placental tissue at term labour. PGHS-2 protein levels in sheep placenta were significantly higher than those of PGHS-1 in all intrauterine tissues examined. This result supports the hypothesis that PGHS-2 is a major contributor to PG formation at term labour. To elucidate the developmental changes in PGHS-1 and PGHS-2 relative to labour onset, an experimental paradigm of glucocorticoid-induced delivery was used. Previous characterisation and validation of this labour model demonstrated that direct, transabdominal, intrafetal injection of the synthetic glucocorticoid betamethasone (5.7 mg in 1 ml aqueous vehicle) on day 131 of gestation induced labour onset in 56.6+/-0.8 h (mean+/-s.e.m.). As the latent period to induced-labour was known, the time course of enzyme formation could be ascertained. Sheep (n=20) were killed by barbiturate injection at various time intervals post-injection (0, 14, 28, 42 and 56 h). Tissue extracts collected at post-mortem examination were prepared and analysed by Western blots. PGHS-2 was induced in ovine cotyledon in a time-dependent fashion following glucocorticoid injection (P<0.05). There was a 12-fold increase in abundance between the time of betamethasone administration (0 h) and established labour (56 h). The PGHS-2 isozyme was not detected in any of the other tissues examined. In contrast, formation of the PGHS-1 isozyme did not change in relation to induced-labour in any of the intrauterine tissues. This finding is consistent with constitutive formation of PGHS-1. Previous studies have demonstrated a rise in PG production in association with glucocorticoid-induced labour and spontaneous delivery. The results of the present study indicate that this rise in PG production is due to increased formation of the PGHS-2 isozyme in ovine cotyledon. PGHS-2 appears to be induced by exogenous glucocorticoid administration and/or the mechanisms controlling ovine parturition. The role of PG formation by the fetal membranes is yet to be elucidated.

Measurement of interleukin-1 alpha and interleukin-6 in pregnancy-associated tissues

1996 ◽  
Vol 8 (7) ◽  
pp. 1069 ◽  
Author(s):  
L Gunn ◽  
P Hardiman ◽  
S Tharmaratnam ◽  
D Lowe ◽  
T Chard
Keyword(s):  
Amniotic Fluid ◽  
Interleukin 1 ◽  
Elective Caesarean Section ◽  
Maternal Blood ◽  
Fetal Membranes ◽  
Fetal Blood ◽  
Tissue Extracts ◽  
Arterial Blood ◽  
Term Labour ◽  
In Pregnancy

The concentrations of interleukin-1 alpha (IL-1 alpha) and IL-6 in pregnancy-associated tissues were investigated in term labour and delivery in the absence of labour (elective Caesarean section). Samples of amniotic fluid, placenta, fetal membranes, umbilical venous and, where possible, umbilical arterial blood were collected at delivery (37-41 weeks of gestation). Maternal blood was sampled during labour. Fluid and tissue extracts were assayed for IL-1 alpha and IL-6 by radioimmunoassay. Placenta and membranes were examined histologically for evidence of infection. Concentrations of IL-1 alpha and IL-6 in amniotic fluid and membrane extract, and IL-1 alpha in maternal and fetal blood, were raised after the onset of labour. Concentrations of both cytokines in the placenta remained unchanged. There was a good correlation between concentrations of both cytokines in amniotic fluid and membranes. There was also a significant correlation between concentrations of IL-1 alpha and IL-6 in amniotic fluid, placenta and membranes. It is suggested that the fetal membranes or maternal decidua, but not the placenta, internal fetal or maternal tissues, are the main sources of IL-1 alpha and IL-6 during labour.

scholarly journals 1,25-dihydroxyvitamin D3 production and vitamin D3 receptor expression are developmentally regulated during differentiation of human monocytes into macrophages

Blood ◽  
1993 ◽  
Vol 82 (4) ◽  
pp. 1300-1307 ◽  
Author(s):  
M Kreutz ◽  
R Andreesen ◽  
SW Krause ◽  
A Szabo ◽  
E Ritz ◽  
...  
Keyword(s):  
Vitamin D3 ◽  
In Vitro Maturation ◽  
Time Course ◽  
Interleukin 1 ◽  
Mononuclear Phagocytes ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Ifn Gamma ◽  
Dihydroxyvitamin D3

Abstract It has been well established that human mononuclear phagocytes have the capacity to produce 1,25-dihydroxy-vitamin D3 [1,25(OH)3D3] and express the vitamin D receptor (VDR). However, 1 alpha-hydroxylase activity and VDR receptor expression during differentiation of monocytes (MO) into mature macrophages (MAC) have not been previously examined. The in vitro maturation of blood MO can serve as a model for the in vivo transformation of immature blood MO into MAC. Here, when cultured in the presence of serum, MO undergo characteristic changes in morphology, antigenic phenotype, and functional activity consistent with their differentiation into MAC. We serially measured 1,25(OH)2D3 and 24,25- dihydroxyvitamin D3 [24,25(OH)2D3] synthesis, specific [3H]-1,25(OH)2D3 binding, and VDR mRNA levels during in vitro maturation of MO into MAC and correlated these functions with maturation-associated changes in the phenotype (MAX.1 and CD71) and secretory repertoire (interleukin-1 beta [IL-1 beta], neopterin) of the cells. MO showed only little conversion of 25-(OH)D3 into 1,25(OH)2D3 (1.4 +/- 0.4 pmol/10(6) cells/6 h, n = 5) that increased gradually during maturation into MAC at day 8 of culture (5.3 +/- 4.3 pmol/10(6) cells/6 h, n = 5). Interferon-gamma (IFN-gamma) increased baseline 1,25(OH)2D3-synthesis approximately twofold during all phases of differentiation. The time course of increased 1,25(OH)2D3-synthesis correlated with enhanced secretion of neopterin and expression of MAX.1 and CD71. The addition of exogenous 1,25(OH)2D3 did not influence constitutive 1,25(OH)2D3 synthesis, but IFN-gamma-stimulated production was suppressed to baseline levels. Exogenous 1,25(OH)2D3 also stimulated 24,25(OH)2D3 synthesis in freshly isolated MO (from 1.0 +/- 0.8 pmol/6 h to 5.6 +/- 0.9 pmol), whereas matured MAC showed no 24,25(OH)2D3 synthesis. Furthermore, we examined the expression of the VDR during the differentiation process. VDR mRNA and protein were constitutively expressed in MO, whereas VDR was downregulated in mature MAC on both the mRNA and protein levels. Homologous upregulation of VDR protein by 1,25(OH)2D3 occurred in MO and, to a lesser degree, in MAC. In contrast, VDR mRNA concentrations were not influenced by 1,25(OH)2D3. Taken together, our results show that MO into MAC differentiation in vitro is associated with (1) an enhanced capacity to synthesize 1,25(OH)2D3, (2) a loss of 24,25(OH)2D3-synthesizing activity, and (3) a decrease in the expression of VDR mRNA and protein. Because 1,25(OH)2D3 was shown to induce differentiation of MO into MAC, our data sugest an autoregulatory mechanism of MO/MAC generation by 1,25(OH)2D3.

scholarly journals Genetic and metabolic status of NGF-deprived sympathetic neurons saved by an inhibitor of ICE family proteases.

1996 ◽  
Vol 135 (5) ◽  
pp. 1341-1354 ◽  
Author(s):  
M Deshmukh ◽  
J Vasilakos ◽  
T L Deckwerth ◽  
P A Lampe ◽  
B D Shivers ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Time Course ◽  
Sympathetic Neurons ◽  
Interleukin 1 ◽  
Cysteine Proteases ◽  
Interleukin 1 Beta ◽  
A Cell ◽  
Genetic Events ◽  
Time Point

Sympathetic neurons undergo programmed cell death (PCD) when deprived of NGF. We used an inhibitor to examine the function of interleukin-1 beta-converting enzyme (ICE) family proteases during sympathetic neuronal death and to assess the metabolic and genetic status of neurons saved by such inhibition. Bocaspartyl(OMe)-fluoromethylketone (BAF), a cell-permeable inhibitor of the ICE family of cysteine proteases, inhibited ICE and CPP32 (IC50 approximately 4 microM) in vitro and blocked Fas-mediated apoptosis in thymocytes (EC50 approximately 10 microM). At similar concentrations, BAF also blocked the NGF deprivation-induced death of rat sympathetic neurons in culture. Compared to NGF-maintained neurons, BAF-saved neurons had markedly smaller somas and maintained only basal levels of protein synthesis; readdition of NGF restored growth and metabolism. Although BAF blocked apoptosis in sympathetic neurons, it did not prevent the fall in protein synthesis or the increase in the expression of c-jun, c-fos, and other mRNAs that occur during neuronal PCD, implying that the ICE-family proteases function downstream of these events during PCD.NGF and BAF rescued sympathetic neurons with an identical time course, suggesting that NGF, in addition to inhibiting metabolic and genetic events associated with neuronal PCD, can act posttranslationally to abort apoptosis at a time point indistinguishable from the activation of cysteine proteases. Both poly-(ADP ribose) polymerase and pro-ICE and Ced-3 homolog-1 (ICH-1) appear to be cleaved in a BAF-inhibitable manner, although the majority of pro-CPP32 appears unchanged, suggesting that ICH-1 is activated during neuronal PCD. Potential implications of these findings for anti-apoptotic therapies are discussed.

scholarly journals Time Course of Ethylene Thiourea in Maternal Plasma, Amniotic Fluid and Embryos in Rats Following Single Oral Dosing.

1996 ◽  
Vol 58 (12) ◽  
pp. 1235-1236 ◽  
Author(s):  
Takayuki IWASE ◽  
Masako YAMAMOTO ◽  
Mitsuyuki SHIRAI ◽  
Fumiaki AKAHORI ◽  
Toshio MASAOKA ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Time Course ◽  
Maternal Plasma ◽  
Oral Dosing ◽  
Ethylene Thiourea

Tumour necrosis factor a during human pregnancy and labour: maternal plasma and amniotic fluid concentrations and release from intrauterine tissues

1994 ◽  
Vol 131 (6) ◽  
pp. 607-614 ◽  
Author(s):  
Nihay Laham ◽  
Shaun P Brennecke ◽  
Klaus Bendtzen ◽  
Gregory E Rice
Keyword(s):  
Amniotic Fluid ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Preterm Labour ◽  
Maternal Plasma ◽  
Tnf Α ◽  
Factor Α ◽  
Stimulating Factor ◽  
Necrosis Factor

Laham N, Brennecke SP, Bendtzen K, Rice GE. Tumour necrosis factor α during human pregnancy and labour: maternal plasma and amniotic fluid concentrations and release from intrauterine tissues. Eur J Endocrinol 1994;131:607–14. ISSN 0804–4643 The aims of this study were: to quantify immunoreactive tumour necrosis factor α (TNF-α) concentrations in maternal plasma and amniotic fluid obtained from women during pregnancy and labour, both at term and preterm; and to establish the effects of bacterial endotoxin and cytokines on the in vitro release of TNF-α from intrauterine tissues. Maternal plasma TNF-α concentrations did not change during pregnancy (457.2 ± 102.9 ng/l, mean ± sem, N = 52) or at the time of labour (543.5 ± 138.6 ng/l, N = 43). In contrast, amniotic fluid TNF-α concentrations increased significantly (p < 0.05) during pregnancy (early pregnancy, EP, 93.0 ± 24.8 ng/l, N = 7; preterm not-in-labour, PNIL, 186.8 ± 42.9 ng/l, N = 16; term not-in-labour, TNIL, 499.7 ± 150.9 ng/l, N = 13) and in association with preterm labour (preterm in-labour, PIL, 958.7 ± 575.6 ng/l, N = 5 vs PNIL, 186.8 ± 42.9 ng/l, N = 16). Choriodecidual and placental explants (N = 3) maintained in in vitro culture released TNF-α Furthermore, the release of TNF-α-α was increased significantly (p < 0.05) by bacterial endotoxin (lipopolysaccharide, 10 ng/l–10 mg/l) but was not affected by the following cytokines at the indicated doses: interleukin-1α (0.28 nmol/l), interleukin-6 (12.5 nmol/l), granulocyte colony-stimulating factor (2.5 nmol/l), granulocyte–macrophage colonystimulating factor (35 nmol/l), macrophage colony-stimulating factor (1.2 nmol/l), leukaemia inhibitory factor (0.45 nmol/l) and transforming growth factor-β (0.4 nmol/l). The data obtained in this study are consistent with a role for TNF-α in both preterm labour and normal labour at term. N Laham, Department of Perinatal Medicine, Royal Women's Hospital, 132 Grattan Street, Carlton, Victoria, Australia 3053

scholarly journals 1,25-dihydroxyvitamin D3 production and vitamin D3 receptor expression are developmentally regulated during differentiation of human monocytes into macrophages

Blood ◽  
1993 ◽  
Vol 82 (4) ◽  
pp. 1300-1307 ◽  
Author(s):  
M Kreutz ◽  
R Andreesen ◽  
SW Krause ◽  
A Szabo ◽  
E Ritz ◽  
...  
Keyword(s):  
Vitamin D3 ◽  
In Vitro Maturation ◽  
Time Course ◽  
Interleukin 1 ◽  
Mononuclear Phagocytes ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Ifn Gamma ◽  
Dihydroxyvitamin D3

It has been well established that human mononuclear phagocytes have the capacity to produce 1,25-dihydroxy-vitamin D3 [1,25(OH)3D3] and express the vitamin D receptor (VDR). However, 1 alpha-hydroxylase activity and VDR receptor expression during differentiation of monocytes (MO) into mature macrophages (MAC) have not been previously examined. The in vitro maturation of blood MO can serve as a model for the in vivo transformation of immature blood MO into MAC. Here, when cultured in the presence of serum, MO undergo characteristic changes in morphology, antigenic phenotype, and functional activity consistent with their differentiation into MAC. We serially measured 1,25(OH)2D3 and 24,25- dihydroxyvitamin D3 [24,25(OH)2D3] synthesis, specific [3H]-1,25(OH)2D3 binding, and VDR mRNA levels during in vitro maturation of MO into MAC and correlated these functions with maturation-associated changes in the phenotype (MAX.1 and CD71) and secretory repertoire (interleukin-1 beta [IL-1 beta], neopterin) of the cells. MO showed only little conversion of 25-(OH)D3 into 1,25(OH)2D3 (1.4 +/- 0.4 pmol/10(6) cells/6 h, n = 5) that increased gradually during maturation into MAC at day 8 of culture (5.3 +/- 4.3 pmol/10(6) cells/6 h, n = 5). Interferon-gamma (IFN-gamma) increased baseline 1,25(OH)2D3-synthesis approximately twofold during all phases of differentiation. The time course of increased 1,25(OH)2D3-synthesis correlated with enhanced secretion of neopterin and expression of MAX.1 and CD71. The addition of exogenous 1,25(OH)2D3 did not influence constitutive 1,25(OH)2D3 synthesis, but IFN-gamma-stimulated production was suppressed to baseline levels. Exogenous 1,25(OH)2D3 also stimulated 24,25(OH)2D3 synthesis in freshly isolated MO (from 1.0 +/- 0.8 pmol/6 h to 5.6 +/- 0.9 pmol), whereas matured MAC showed no 24,25(OH)2D3 synthesis. Furthermore, we examined the expression of the VDR during the differentiation process. VDR mRNA and protein were constitutively expressed in MO, whereas VDR was downregulated in mature MAC on both the mRNA and protein levels. Homologous upregulation of VDR protein by 1,25(OH)2D3 occurred in MO and, to a lesser degree, in MAC. In contrast, VDR mRNA concentrations were not influenced by 1,25(OH)2D3. Taken together, our results show that MO into MAC differentiation in vitro is associated with (1) an enhanced capacity to synthesize 1,25(OH)2D3, (2) a loss of 24,25(OH)2D3-synthesizing activity, and (3) a decrease in the expression of VDR mRNA and protein. Because 1,25(OH)2D3 was shown to induce differentiation of MO into MAC, our data sugest an autoregulatory mechanism of MO/MAC generation by 1,25(OH)2D3.

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