Biomedical subjects

F Ietta

Publications and source records attributed to F Ietta.

5 recordsLinked to original sources

PubMed2005

A novel Mtd splice isoform is responsible for trophoblast cell death in pre-eclampsia.

Pre-eclampsia is a serious disorder of human pregnancy, characterized by decreased utero-placental perfusion and increased trophoblast cell death. Presently, the mechanisms regulating trophoblast cell death in pre-eclampsia are not fully elucidated. Herein, we have identified a novel Mtd/Bok splice isoform (Mtd-P) resulting from exon-II skipping. Mtd-P expression was unique to early-onset severe pre-eclamptic placentae as assessed by quantitative real-time-PCR and immunoblotting. Mtd-P overexpression in cell lines (BeWo: cytotrophoblast-derived; and CHO: ovary-derived) resulted in increased apoptotic cell death as assessed by caspase-3 cleavage, internucleosomal DNA laddering and mitochondrial depolarization. Moreover, Mtd-P expression increased under conditions of low oxygenation/oxidative stress in human villous explants. Antisense knockdown of Mtd under conditions of oxidative stress resulted in decreased caspase-3 cleavage. We conclude that under conditions of reduced oxygenation/oxidative stress, Mtd-P causes trophoblast cell death in pre-eclampsia and hence may contribute to the molecular events leading to the clinical manifestations of this disease.

Alternative Splicing↗

PubMed2003

Expression of macrophage migration inhibitory factor in diffuse systemic sclerosis.

OBJECTIVE: To evaluate whether, in patients with the diffuse form of systemic sclerosis (dSSc), macrophage migration inhibitory factor (MIF) production is dysregulated. METHODS: 10 patients with dSSc and 10 healthy controls, matched for age and sex, were studied. MIF expression was evaluated by immunohistochemistry on formalin fixed skin biopsies of patients with dSSc and controls. MIF levels were assayed in the sera and in the supernatants of skin cultured fibroblasts by a colorimetric sandwich enzyme linked immunosorbent assay (ELISA). MIF concentrations in culture medium samples and in serum samples were compared by Student's two tailed t test for unpaired data. RESULTS: Anti-MIF antibody immunostained the basal and mainly suprabasal keratinocytes. Small perivascular clusters of infiltrating mononuclear cells were positive; scattered spindle fibroblast-like cells were immunostained in superficial and deep dermal layers. The serum concentrations of MIF in patients with dSSc (mean (SD) 10705.6 (9311) pg/ml) were significantly higher than in controls (2157.5 (1288.6) pg/ml; p=0.011); MIF levels from dSSc fibroblast cultures (mean (SD) 1.74 (0.16) ng/2 x 10(5) cells) were also significantly higher than in controls (0.6 (0.2) ng/2 x 10(5) cells; p=0.008). CONCLUSION: These results suggest that MIF may be involved in the amplifying proinflammatory loop leading to scleroderma tissue remodelling.

Adult↗

PubMed2002

Macrophage migration inhibitory factor in human pregnancy and labor.

PROBLEM: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in reproduction. Presently there is no information on the possible involvement of MIF in the onset of labor. METHODS: Macrophage migration inhibitory factor was assayed, by enzyme-linked immunosorbent assay (ELISA), in maternal serum (MS) and amniotic fluid (AF) both, at midtrimester and at term, as well as in cord serum (CS) at birth. Extraembryonic membranes were analyzed by immunohistochemistry. RESULTS: Amniotic fluid MIF concentrations were significantly higher at term (median 62.10 ng/mL) than at midtrimester (median 20.07 ng/mL) and reached a peak in term labor (median 258.80 ng/mL). The AF/MS ratio varied from a median of 4.34 at midtrimester and 33.7 at term labor. The MS/CS ratio was 0.4. Migration inhibitory factor immunoreactivity was found in different cell layers of the extraembryonic membranes. CONCLUSIONS: The increased secretion of MIF in AF at term, particularly at term labor, suggests that MIF contributes to the inflammatory events leading to labor.

Adult↗

PubMed2002

Interferons and their receptors in human papillomavirus lesions of the uterine cervix.

PURPOSE OF INVESTIGATION: In this study we analyzed the immunohistochemical expression of specific types of interferon (IFN) in human papillomavirus (HPV) associated cervical lesions. METHODS: Reactivity to anti-IFN-alpha,-beta and -gamma and to anti-IFN-alpha/beta- and gamma-receptors was tested in 33 cervical punch biopsies from 24 HPV-infected women and nine healthy controls. The HPV-infected cases were subdivided into low-risk and high-risk groups, according to the known "oncogenic" potential of the HPV-types detected by PCR. RESULTS: Cervical epithelium and stroma in HPV-negative as well as low-risk HPV-positive samples were diffusely stained by anti IFN-alpha, beta and gamma antibodies. In contrast, a significantly lower percentage of high-risk HPV-infected tissues was immunoreactive to IFN-beta in the stroma and IFN-gamma in the epithelium. There were no relevant differences between control and HPV cases in the expression of IFN-receptors. CONCLUSION: We show that a decreased production of some specific classes of IFN is associated with high-risk-type HPV lesions suggesting an important role of IFN distribution patterns in the pathogenesis of HPV lesions.

Adult↗

PubMed2001

Macrophage migration inhibitory factor in the human endometrium: expression and localization during the menstrual cycle and early pregnancy.

Macrophage migration inhibitory factor (MIF) was discovered as an activated T-lymphocyte-derived protein that inhibits the random migration of macrophages in vitro. Subsequently, knowledge of the physiological actions of MIF was extended to include its role as a proinflammatory cytokine that affects several functions of macrophages and lymphocytes. Previous reports have suggested an involvement of MIF in reproduction. However, no data are currently available on the presence of this cytokine in the human endometrium. In this study, the expression and tissue localization of MIF was evaluated in specimens of cycling endometrium, first trimester placenta bed biopsy, and isolated endometrial glands by Western blot analysis, immunohistochemistry, ELISA, and reverse transcription-polymerase chain reaction. The results demonstrated that MIF is expressed in human endometrium across the menstrual cycle and in early pregnancy. Immunohistochemical localization identified the protein in glandular epithelium, in stromal and predecidualized stromal cells of cycling endometrium, as well as in the decidua of first-trimester placenta. The proinflammatory features and specific actions of MIF on lymphoid cells suggest its potential involvement in several aspects of endometrial physiology.

Blotting, Western↗