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J M Vinci

Publications and source records attributed to J M Vinci.

14 recordsLinked to original sources
PubMed2001

Localization and regulation of IL-1alpha in rat myometrium during late pregnancy and the postpartum period.

Interleukin-1 (IL-1) has been implicated as a participant in preterm labor that is induced by bacterial infection. Previously, we showed that serotonin-induced production of IL-1alpha by myometrial smooth muscle cells in vitro is also essential for the synthesis of interstitial collagenase. It is therefore likely that IL-1alpha production in uterine tissues has implications for both the normal physiology of involution and for the pathophysiological mechanisms of preterm labor. The objective of this study was to characterize the serotonin-induced production of IL-1alpha by myometrial cultures in vitro and to assess the production of IL-1alpha and its relationship to collagenase production in vivo during pregnancy and the postpartum period. Immunohistochemistry demonstrated IL-1alpha protein in the nuclei and cytoplasm of serotonin-treated myometrial cells. IL-1alpha levels were decreased by treatment with progesterone or IL-1-receptor antagonist but were unaffected by lipopolysaccharide. Western analysis of myometrium from pregnant rats showed low levels of IL-1alpha during midpregnancy with increased concentrations at days 21 and 22 and postpartum. IL-1alpha mRNA levels also increased from days 15 to 22. Levels of mRNA for IL-1beta also increased, although to a lesser degree than IL-1alpha. Both mRNAs decreased postpartum. Conversely, mRNA for interstitial collagenase was barely detectable at term but increased postpartum. Together, these data show that serotonin stimulates IL-1alpha production in vitro and indicate that normal myometrium from pregnant rats is an identifiable source of IL-1 during late pregnancy. The findings are consistent with the possibility that myometrial IL-1alpha participates in normal labor as well as the postpartum production of interstitial collagenase.

Animals↗
PubMed1999

Progesterone mediates decreases in uterine smooth muscle cell interleukin-1alpha by a mechanism involving decreased stability of IL-1alpha mRNA.

The regulation, by progesterone, of serotonin-induced interleukin-1alpha production was studied in primary cultures of rat uterine smooth muscle cells. Prior reports from this laboratory have demonstrated that these cells produce IL-1alpha and IL-1beta mRNAs in response to the hormonal action of serotonin. Results of the present study indicate that treatment of myometrial smooth muscle cells with medroxyprogesterone acetate (MPA) results in a marked decrease in IL-1alpha protein as measured by western blot analysis. These decreases occur even in the presence of maximally-inducing concentrations of serotonin. MPA-mediated changes in IL-1alpha protein are characterized by a rapid decline in IL-1alpha mRNA levels. This inhibition by medroxyprogesterone also occurs when cells are stimulated to produce IL-1alpha by PMA rather than serotonin. Thus, when cells are cultured in the presence of both inducer and inhibitor, the inhibitor, progesterone, clearly dominates in the control of IL-1alpha expression. This effect is concentration-dependent, can be mimicked by native progesterone or glucocorticoids, but is unaffected by estradiol. The ability of progestins to decrease IL-1alpha mRNA is blocked by both inhibitors of transcription and translation and by treatment with RU-486. Progesterone had no effect on chloramphenicol acetyl transferase (CAT) transcription from two different IL-1alpha promoter constructs, indicating that progesterone's action appears to be dependent on post-transcriptional rather than transcriptional regulation. Conversely, progesterone accelerated the normal rate of decay of IL-1alpha mRNA that occurs following the removal of serotonin from the cultures. These results suggest that progesterone decreases IL-1alpha levels by stimulating the production of an intracellular intermediate that decreases the stability of IL-1alpha mRNA.

Animals↗
PubMed1999

Serotonin-inducible transcription of interleukin-1alpha in uterine smooth muscle cells requires an AP-1 site: cloning and partial characterization of the rat IL-1alpha promoter.

Interleukin-1 has been shown to contribute to infection-induced inflammatory processes during pregnancy. Prior work from this laboratory has demonstrated that serotonin-induced IL-1alpha also is required for the in-vitro production of collagenase in uterine smooth muscle cells, a normal, non-inflammatory process that occurs in-vivo during post-partum uterine involution. To understand the molecular mechanisms that regulate transcription of the IL-1alpha gene in these cells, we isolated and characterized 1.6 kilobases of the 5'-flanking region of the rat IL-1alpha gene. Sequencing and primer extension identified a single transcription start site and multiple potential regulatory elements, including a TATA box at - 30 bp, a CAAT box at - 74 bp, and a conserved AP-1 site at - 9 bp. This 5'-flanking DNA exhibited low basal promoter activity that was inducible by serotonin. Serotonin-induced promoter activity was unaffected or induced by either medroxyprogesterone or IL-1 receptor antagonist. This occurred despite the ability of both of these hormones to markedly decrease IL-1alpha mRNA. Deletional analysis revealed a strong repressor in the region between - 147 and - 98 bp; removal of this sequence resulted in a fivefold higher basal promoter activity that was still serotonin responsive. Constitutive promoter activity appeared to reside between - 97 and - 22 bp. Deletion of this promoter region, which contained the TATA and CAAT boxes and an NF-IL-6/PEA-3 site, resulted in decreased basal transcriptional activity to the low level seen in larger constructs. Mutational analysis showed that serotonin-inducible transcriptional activity was mediated, at least in part, by the conserved AP-1 site at - 9 bp. This site is located within a larger extended palindromic region: 5'-AAGCCTGACTCAGACTT-3', that together effects both the basal and serotonin-inducible expression of the IL-1alpha gene.

Animals↗
PubMed1998

Decreased tyrosine phosphorylation of focal adhesion kinase after estradiol treatment of MCF-7 human breast carcinoma cells.

MCF-7 human breast carcinoma cultures grown in the presence of 17-beta estradiol form solid, multicellular nodules, a process that reflects changes in cell-substrate adhesions and loss of growth inhibition. We examined the effects of estradiol on the status of tyrosine phosphorylation in focal adhesion kinase (FAK) and the association of FAK with paxillin using immunoprecipitations and then probing western blots for FAK, phosphotyrosine, and paxillin. Culture of MCF-7 cells for seven days in the presence of 1 nM E2 resulted in decreased tyrosine phosphorylation of FAK compared to controls. The estradiol-induced effect was blocked by 100 nM of the estrogen receptor antagonist 4-hydroxytamoxifen, indicating dephosphorylation of FAK is an estrogen receptor-mediated event. FAK immunoprecipitated from either estradiol or DMSO-treated cells phosphorylated the exogenous substrate poly(Glu,Tyr), suggesting that the potential kinase activity of FAK was not changed by estradiol. Estradiol treatment also resulted in a reduced association between FAK and paxillin. The decreased phosphorylation levels and reduced association between FAK and paxillin may be important steps leading to the loss of stable focal contacts and loss of growth inhibition during MCF-7 nodulation.

Breast Neoplasms↗
PubMed1993

Expression of messenger RNAs for complement inhibitors in human tissues and tumors.

The mRNAs coding for three complement inhibitors produced by human cells, complement cytolysis inhibitor (CLI), decay-accelerating factor (DAF), and CD59, are characteristically distributed among normal tissues. High levels of CLI mRNA are expressed in tissues that express low levels of DAF mRNA and vice versa. Therefore, the expression of these mRNAs shows a mutually exclusive relationship, with the possible exception of the lung, where all these mRNAs are expressed. In contrast, CD59 mRNA is rather uniformly expressed in all tumor cell lines examined, whereas the mRNA for either of the two other complement inhibitors is overexpressed in some specific tumor cells, e.g., HeLa cells overexpress DAF mRNA, while A172 cells overexpress CLI mRNA. These two cell lines were resistant to antibody-dependent complement cytotoxicity. Expression of CLI and DAF mRNA was induced in cells treated with the antitumor drug N-(chloroetyl)-N'-cyclohexyl-N-nitrosourea; these cells became resistant to complement cytotoxicity. A similar pattern of expression was detected in tumor samples obtained during surgery, with a relatively uniform expression of CD59 mRNA and occasional overexpression of CLI or DAF mRNA. These findings suggest that overexpression of complement inhibitors mRNA and of the corresponding proteins may contribute to tumor cell resistance to complement-mediated cytotoxicity.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1991

The AU-rich sequences in the 3' untranslated region mediate the increased turnover of interferon mRNA induced by glucocorticoids.

Different vectors were constructed that expressed the human interferon-beta (IFN-beta) mRNA constitutively and contained various deletions in the 3' untranslated region (UTR). AU-rich sequences in the 3' UTR were specifically deleted in two vectors. Cell lines secreting human IFN-beta were established by transfecting murine L929 cells with the vectors. These cells showed similar levels of IFN-beta mRNA and secreted comparable amounts of IFN-beta, indicating that the deletion of AU-rich sequences had no effect on the stability and little effect on the efficiency of translation of this mRNA. The synthetic glucocorticoid dexamethasone was previously shown to increase the turnover of IFN-beta mRNA. This activity of dexamethasone was clearly observed only in cells expressing IFN-beta mRNA with AU-rich sequences in the 3' UTR. The increased turnover of this mRNA occurred in the presence of cycloheximide; therefore, it did not require synthesis of new proteins. These findings suggest that glucocorticoids may activate a ribonuclease that degrades mRNAs containing AU-rich sequences in the 3' UTR.

Adenine↗
PubMed1981

Renal vasoactive hormones in scleroderma (progressive systemic sclerosis).

Plasma renin activity and the urinary excretions of kallikrein, kinin, immunoreactive PGE (iPGE) and aldosterone were determined in 23 patients with progressive systemic sclerosis (PSS) on a fixed sodium and potassium intake who had no clinically apparent renal disease. Urinary excretions of kallikrein and kinin in the PSS patients were not significantly different from those of a group of sex and race-matched normal controls. In the female PSS patients urinary excretion of iPGE was also found to be normal. Upright PRA was appropriate for the urinary sodium excretion in 18 PSS patients (13 normotensive and 5 hypertensives) but was significantly elevated in the remaining 5 (all normotensive). The data suggest that the renal kallikrein-kinin and prostaglandin systems are unaltered in PSS patients without clinical evidence of renal disease.

Adult↗
PubMed1979

Effect of indomethacin and adrenocorticotrophic hormone on renal function in man: an experimental model of inappropriate antidiuresis.

The effect of prostaglandin synthesis inhibition on basal and ACTH-stimulated adrenal and renal function was investigated in normal volunteers. Data were collected during control and experimental study periods (13 days each). Adrenocorticotrophic hormone (Cosyntropin, 80 U/day) was administered i.v. on days 8 and 9 of each period. Indomethacin (150 mg/day) was given on days 5 through 13 of the experimental period. The subjects ate a constant diet containing 9 mEq of sodium, 100 mEq of potassium, and 2,500 ml of fluid daily. Indomethacin markedly inhibited urinary PGE excretion and plasma PGE concentration. The effect of ACTH alone as compared to the effect of ACTH and indomethacin showed: plasma sodium concentration, 139 +/- 1 vs. 131 +/ 3 mEg/liter (P less than 0.01, mean +/- SEM); plasma osmolality, 287 +/- 3 vs. 270 +/- 3 mOsm/liter (P less than 0.01); free water clearance, 97 +/- 66 vs. -1100 +/- 380 ml/24hr (P less than 0.01); urine volume, 2,000 +/- 60 vs. 950 +/- 200 ml/day (P less than 0.01); and urine osmolality 282 +/- 12 vs. 720 +/- 144 mOsm/liter (P less than 0.01). We conclude that the effects of ACTH and prostaglandin synthesis inhibition interact to result in inappropriate antidiuresis.

Adrenal Glands↗
PubMed1979

Relationship of human urinary and plasma kinins to sodium-retaining steroids and plasma renin activity.

In these studies we have shown that: 1. urinary kallikrein is an index of sodium-retaining steroid activity and may participate in the anti-natriuretic and kaliuretic effects of these hormones; 2. urinary kinin excretion is independent of changes in urinary kallikrein excretion; 3. levels of plasma bradykinin are highly correlated with levels of plasma renin activity probably because both respond to changes in extracellular fluid volume; and, 4. plasma bradykinin may act to antagonize angiotensin II to maintain normal blood pressure in hyper-reninemic states.

Adolescent↗
PubMed1978

The kallikrein-kinin system in Bartter's syndrome and its response to prostaglandin synthetase inhibition.

The kallikrein-kinin system was characterized in seven patients with Bartter's syndrome on constant metabolic regimens before, during, and after treatment with prostaglandin synthetase inhibitors. Patients with Bartter's syndrome had high values for plasma bradykinin, plasma renin activity (PRA), urinary kallikrein, urinary immunoreactive prostaglandin E excretion, and urinary aldosterone; urinary kinins were subnormal and plasma prekallikrein was normal. Treatment with indomethacin or ibuprofen which decreased urinary immunoreactive prostaglandin E excretion by 67%, decreased mean PRA (patients recumbent) from 17.3+/-5.3 (S.E.M.) ng/ml per h to 3.3+/-1.1 ng/ml per h, mean plasma bradykinin (patients recumbent) from 15.4+/-4.4 ng/ml to 3.9+/-0.9 ng/ml, mean urinary kallikrein excretion from 24.8+/-3.2 tosyl-arginine-methyl ester units (TU)/day to 12.4+/-2.0 TU/day, but increased mean urinary kinin excretion from 3.8+/-1.3 mug/day to 8.5+/-2.5 mug/day. Plasma prekallikrein remained unchanged at 1.4 TU/ml. Thus, with prostaglandin synthetase inhibition, values for urinary kallikrein and kinin and plasma bradykinin returned to normal pari passu with changes in PRA, in aldosterone, and in prostaglandin E. The results suggest that, in Bartter's syndrome, prostaglandins mediate the low urinary kinins and the high plasma bradykinin, and that urinary kallikrein, which is aldosterone dependent, does not control kinin excretion. The high plasma bradykinin may be a cause of the pressor hyporesponsiveness to angiotensin II which characterizes the syndrome.

Adolescent↗
PubMedDate not supplied

Expression of interleukin-1 alpha and beta in early passage fibroblasts from aging individuals.

Human diploid fibroblasts (HDFs) from newborn foreskin constitutively express interleukin-1 (IL-1) mRNA and protein after completing at least 70% (approximately 40 population doublings) of their in vitro life span. This IL-1 in turn induces the synthesis of specific proteins in aging HDFs. To determine whether IL-1 expression may be promoted by in vivo aging, we analyzed the expression of IL-1 and of inducible mRNAs in HDFs from two normal individuals 55 and 92 years old and in HDFs from a patient with premature aging caused by Werner's syndrome. By reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), we detected expression of IL-1 alpha and beta mRNA and protein in early passage HDFs from both normal individuals and the Werner's syndrome patient. These HDFs also expressed the IL-1-inducible mRNAs for stromelysin, plasminogen activator inhibitor type 2, manganous superoxide dismutase, and collagenase. These results suggest that an age-dependent expression of IL-1 occurs either in vivo or after a few cell divisions in vitro. Therefore, the fibroblast phenotype is modified by the expression of IL-1-inducible genes during aging.

Aged↗