Fabio D'Amico

University of Catania, Catania, Sicily, Italy

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Publications (29)58.06 Total impact

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    ABSTRACT: Systemic sclerosis is a multifactorial and heterogeneous disease. Genetic and environmental factors are known to interplay in the onset and progression of systemic sclerosis. Sex plays an important and determinant role in the development of such a disorder. Systemic sclerosis shows a significant female preponderance. However, the reason for this female preponderance is incompletely understood. Hormonal status, genetic and epigenetic differences, and lifestyle have been considered in order to explain female preponderance in systemic sclerosis. Sex chromosomes play a determinant role in contributing to systemic sclerosis onset and progression, as well as in its sex-biased prevalence. It is known, in fact, that X chromosome contains many sex- and immuno-related genes, thus contributing to immuno tolerance and sex hormone status. This review focuses mainly on the recent progress on epigenetic mechanisms-exclusively linked to the X chromosome-which would contribute to the development of systemic sclerosis. Furthermore, we report also some hypotheses (dealing with skewed X chromosome inactivation, X gene reactivation, acquired monosomy) that have been proposed in order to justify the female preponderance in autoimmune diseases. However, despite the intensive efforts in elucidating the mechanisms involved in the pathogenesis of systemic sclerosis, many questions remain still unanswered.
    Clinical Reviews in Allergy & Immunology 10/2013; · 5.59 Impact Factor
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    ABSTRACT: A case control study to evaluate the possible influence of FOXP3 polymorphisms (rs3761548 and rs2280883) in the susceptibility of systemic sclerosis in an Italian Caucasian population. Subgroup analysis was also performed to test association between these SNPs and specific disease phenotypes. The study groups consisted of 467 individuals: 228 patients (194 with limited cutaneous form and 34 with diffuse cutaneous form of the disease) and 239 healthy control subjects. Genotyping was performed by high resolution melting analysis. Genotype distribution and allele frequency of the FOXP3 polymorphisms were analyzed statistically, using χ(2) or Fisher exact test. Single-marker analysis of allelic and genotype frequencies revealed that SNP rs3761548 was not associated with systemic sclerosis susceptibility. Analysis of genotype and allele distributions of the rs2280883 genetic variant was associated, only in female subjects with systemic sclerosis, its limited subtype, and anti-centromere autoantibodies. Although these findings require replication in a larger set and other populations, FOXP3 rs2280883 may represent a novel susceptibility locus for systemic sclerosis in female subjects.
    Immunology letters 05/2013; · 2.91 Impact Factor
  • Int J Mol Med. 2013 May;. 05/2013; 5(31):1011-6..
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    ABSTRACT: In this study, we investigated the expression and localisation of the proteins, osteopontin (OPN) and prominin-1 (CD133), as well as the plasma OPN levels in the endometrium of patients with endometriosis. Samples of ectopic endometriotic lesions and normal endometrium were obtained from 31 women with endometriosis and 28 healthy control subjects. The mRNA and protein expression of OPN and CD133 was analysed by real‑time RT-PCR and immunohistochemistry. The plasma levels of OPN were determined by ELISA. Our results revealed that OPN mRNA and protein expression, as well as its release in the blood, was significantly increased in the endometriotic lesions in comparison to normal tissue. Although the presence of CD133+ cells was detected in the normal endometrium, as well as in the endometriosis specimens, a significant quantitative variation of this protein was not demonstrated in the patients with endometriosis. In conclusion, our data indicate that OPN is involved in the development of endometriosis by enhancing the invasiveness, proliferation and survival of endometrial cells in ectopic lesions. CD133 cannot be used as a disease marker for endometriosis, although an involvement of this protein in the pathogenesis of endometriosis cannot be excluded.
    International Journal of Molecular Medicine 03/2013; · 1.96 Impact Factor
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    ABSTRACT: Macrophages as a principal component of immune system play an important role in the initiation, modulation, and final activation of the immune response against pathogens. Upon stimulation with different cytokines, macrophages can undergo classical or alternative activation to become M1 or M2 macrophages, which have different functions during infections. Although chitotriosidase is widely accepted as a marker of activated macrophages and is thought to participate in innate immunity, particularly in defense mechanisms against chitin containing pathogens, little is known about its expression during macrophages full maturation and polarization. In this study we analyzed CHIT-1 modulation during monocyte-to-macrophage maturation and during their polarization. The levels of CHIT-1 expression was investigated in human monocytes obtained from buffy coat of healthy volunteers, polarized to classically activated macrophages (or M1), whose prototypical activating stimuli are interferon-γ and lipopolysaccharide, and alternatively activated macrophages (or M2) obtained by interleukin-4 exposure by real-time PCR and by Western blot analysis. During monocyte-macrophage differentiation both protein synthesis and mRNA analysis showed that CHIT-1 rises significantly and is modulated in M1 and M2 macrophages.Our results demonstrated that variations of CHIT-1 production are strikingly associated with macrophages polarization, indicating a different rule of this enzyme in the specialized macrophages.
    Cell biochemistry and biophysics 11/2012; · 3.34 Impact Factor
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    ABSTRACT: OBJECTIVE: Chronic isoproterenol treatment causes hypertrophy and hyperplasia of rodent salivary glands. Cell-extracellular matrix interactions play a critical role in salivary gland proliferation and matrix metalloproteinases (MMPs) are known to be involved in cell proliferation. The present study was undertaken to investigate the expression of MMP-2 and the tissue inhibitor metalloproteinase (TIMP)-2 in rat parotid gland following isoproterenol treatment. DESIGN: Female Wistar rats were daily treated with isoproterenol (25mg/kg body weight) for 0, 1, 3, and 7 days. Expression of parotid gland MMP-2 and its tissue inhibitor TIMP-2 was analysed by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: Our results suggest that isoproterenol modulates expression of MMP-2 and TIMP-2 mRNAs, as well as their protein expression levels in a time dependent-manner. Interestingly, at day 1 of treatment, MMP-2 and TIMP-2 expression were higher in comparison to untreated gland. At days 3 and 7, we can observe a gradual decrease of mRNA and protein levels of MMP-2 and TIMP-2. CONCLUSIONS: Our results suggest the presence of a isoproterenol-dependent modulation of extracellular matrix components. Such a modulation seems to be associated with β-adrenergic agonist-induced hyperplasy, occurring during the first 24h of agonist treatment, and hypertrophy of the parotid gland.
    Archives of oral biology 09/2012; · 1.65 Impact Factor
  • Arch Oral Biol. 09/2012;
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    Human Immunology 09/2012; 73(9):950-3. · 2.30 Impact Factor
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    ABSTRACT: NECL-5 is involved in regulating cell-cell junctions, in cooperation with cadherins, integrins and platelet-derived growth factor receptor, that are essential for intercellular communication. Its role in malignant transformation was previously described. It has been reported that transformation of melanocytes is associated with altered expression of adhesion molecules suggesting the potential involment of NECL-5 in melanoma development and prognosis. To shed light on this issue, the expression and the role of NECL-5 in melanoma tissues was investigated by bioinformatic and molecular approaches. NECL-5 was up-regulated both at the mRNA and the protein levels in WM35, M14 and A375 cell lines compared with normal melanocytes. A subsequent analysis in primary and metastatic melanoma specimens confirmed "in vitro" findings. NECL-5 overexpression was observed in 53 of 59 (89.8%) and 12 of 12 (100%), primary melanoma and melanoma metastasis, respectively; while, low expression of NECL-5 was detected in 12 of 20 (60%) benign nevi. A significant correlation of NECL-5 overexpression was observed with most of known negative melanoma prognostic factors, including lymph-node involvement (P = 0.009) and thickness (P = 0.004). Intriguingly, by analyzing the large series of melanoma samples in the Xu dataset, we identified the transcription factor YY1 among genes positively correlated with NECL-5 (r = 0.5). The concordant computational and experimental data of the present study indicate that the extent of NECL-5 expression correlates with melanoma progression.
    Oncotarget 08/2012; 3(8):882-92. · 6.64 Impact Factor
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    ABSTRACT: A candidate gene for TIMP-1 gene located on the X-chromosome (rs4898) was selected for a control case study to investigate a possible association of this SNP with the susceptibility to systemic sclerosis and its digit ulcer manifestation. A total of 461 individuals of Italian Caucasian origin (228 SSc patients and 233 healthy control subjects) were genotyped for TIMP-1 +372 T/C single nucleotide polymorphism rs4898. Subgroups were analyzed according to the presence or absence of digital ulcers. The CC genotype and C allele frequencies were significantly lower in female SSc patients than in controls (OR 0.53, CI 0.29-0.96, p=0.03 and OR 0.72, CI 0.53-0.98 p=0.04, respectively). CC genotypes frequency was lower also in female patients with ulcers than those without ulcers (OR 0.37, CI 0.14-1.00, p=0.03). Furthermore, CC genotype and C allele frequencies were lower also in female patients with ulcers in comparison to female healthy control subjects (OR 0.27, CI 0.10-0.70, p=0.004; OR 0.60, CI 0.40-0.89, p=0.01, respectively). The TIMP-1 rs4898 polymorphism may play a protective role in the susceptibility to SSC in females, and in particular to digital ulcer formation.
    Human immunology 07/2012; 73(9):950-3. · 2.55 Impact Factor
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    ABSTRACT: In hepatitis C virus (HCV)-associated liver disease, the immune system is unable to clear the viral infection. Previous studies have raised the possibility of an involvement of regulatory T cells (Tregs). In this study, we analysed the peripheral blood from 30 patients with HCV-associated chronic liver disease and 20 healthy controls by flow cytometry for the evaluation of the Treg population [CD4⁺CD25hi forkhead box protein 3 (Foxp3)⁺], as well as the activated/effector CD4⁺ T cells (CD4⁺CD25low) and IFN-γ-secreting cells. We also analysed liver biopsies of the patients by immunohistochemical evaluation of Foxp3⁺ cells. Our results showed higher proportions of CD4⁺CD25low and IFN-γ⁺ cells in the patients than in the controls. By contrast, the proportions of peripheral CD4⁺CD25hi cells did not significantly differ. The 11 patients displaying Foxp3⁺ cells in the liver infiltrates showed significantly higher proportions of peripheral CD4⁺CD25low cells. Moreover, we found lower serum transaminase levels in the patients than in the controls, as shown by Foxp3⁺ immunohistochemistry, although these results were only statistically significant as regards alanine transaminase (ALT). In conclusion, these data suggest that the presence of Tregs infiltrating the liver is associated with high levels of activated/effector T cells in the peripheral blood and lower activity of hepatitis. Therefore, liver-infiltrating Tregs may play a role in limiting tissue damage and may thus support an effective immune response against HCV.
    International Journal of Molecular Medicine 03/2012; 29(6):983-8. · 1.96 Impact Factor
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    ABSTRACT: MicroRNAs (MiRNAs) are small non-coding RNAs able to regulate gene expression at a posttranscriptional level. Recent evidence indicates that they play a crucial role in the initiation and progression of human cancers. In this review we briefly describe microRNA biogenesis and function, giving a more detailed account of the current state of knowledge concerning the role of microRNAs in brain tumors and stem-like tumor cells. MicroRNAs control brain tumor development by regulating multiple biological characteristics such as proliferation, invasion, differentiation and angiogenesis. Research in this field is rapidly spreading and encourages potential applications of microRNAs as diagnostic and prognostic tools, in addition to therapeutic targets and tools, to grant clinical benefits to patients suffering of brain tumors.
    International Journal of Oncology 12/2011; 40(3):605-24. · 2.66 Impact Factor
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    ABSTRACT: The objective of this study was to determine whether the matrix metalloproteinase-9 (MMP-9) rs3918242 single nucleotide polymorphism may confer susceptibility to systemic sclerosis (SSc) with and without ulcers in an Italian Caucasian population. The MMP-9 rs3918242 functional polymorphism was genotyped in 461 subjects of Italian Caucasian origin: 228 patients with SSc (92 with and 136 without ulcers) and 233 unrelated healthy individuals. The SNP under study was in Hardy-Weinberg equilibrium in the control population. Genotype and allele distributions between SSc patients, with or without ulcers, were not statistically significant (p>0.05). A significant increase of the genotype C/T was observed in male SSc patients without ulcers when compared to patients with ulcers (P=0.04). The MMP-9 rs3918242 functional polymorphism is not associated with susceptibility to SSc. However, the presence of the polymorphism may have a protective effect on the development of ulcers in SSc male patients.
    International Journal of Molecular Medicine 03/2011; 27(6):873-7. · 1.96 Impact Factor
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    ABSTRACT: Prominin-1 (CD133) is a pentaspan cholesterol-binding membrane glycoprotein. Chronic treatment with isoproterenol, a beta-receptor agonist, induces several dramatic effects on salivary glands, such as enhanced DNA synthesis and proliferation of salivary acinar cells. In addition, the biosynthetic pathways of membrane lipids may be altered by the isoproterenol stimulation. The purpose of this study was to investigate the effect of isoproterenol administration on prominin-1 expression profiles in rat parotid gland by means of PCR and immunohistochemistry. Rats were chronically treated with the beta-adrenergic agonist for 1, 3, and 7 days. Our results showed that isoproterenol-treatment caused a down-regulation of prominin-1 on day 3 and 7 of treatment, as well as a differential immunostaining distribution pattern. This study suggests that isoproterenol-treatment may represent a useful tool to explore the molecular mechanisms involved in the synthesis and release of prominin-1. Such efforts could contribute to the development of diagnostic tools based on the detection of prominin-1 in biological fluids, such as saliva.
    International Journal of Molecular Medicine 10/2010; 26(4):505-10. · 1.96 Impact Factor
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    ABSTRACT: Characterization of Treg lymphocytes (CD4+CD25+) in immune response in patients with chronic viral hepatitis C. Two groups of patients were included: Group A (10 patients with chronic hepatitis C); Group B (10 healthy controls). In both groups, liver markers, liver function tests, lymphocyte typing, serum HCV-RNA were assessed. Liver biopsy was executed in Group A only. Peripheral venous samples were analyzed by citofluorimetric analysis, liver biopsy's samples were studied by immunohistochemistry. Group A patients showed a larger expression of Treg (CD4+CD25+) in peripheral blood than Group B with an ipo-expression of a subpopulation of Treg FoxP3+ (CD4+CD25hi). Group B patients showed a higher ratio (CD4+CD25hi/CD4+CD25+) than Group A. Liver biopsy samples showed a clear positivity for FoxP3+ Treg cells in the inflammatory infiltrated. Our study's preliminary results seem to indicate that Treg lymphocytes are really involved in flogistic process in course of chronic hepatitis C. Peripheral blood of infected patients (Group A) shows a low expression of Foxp3+ cells because they are sequestrated in the liver. These cells could be involved in the pathogenesis of the chronic disease and they would be employed how potential agents for a immunomodulatory therapy.
    La Clinica terapeutica 01/2010; 161(3):245-7. · 0.33 Impact Factor
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    ABSTRACT: Non-alcoholic steatohepatitis (NASH) is a progressive fibrotic disease. Many issues related to the pathogenesis of this disease remain unresolved. Because of NASH association with the activation of liver fibrogenesis, we examined the plasma levels and liver immunolocalization of matrix metalloprotease-9 (MMP-9), a molecule involved in the remodelling processes of fibrogenesis. In addition, patients with chronic hepatitis C (HCV) were analyzed. Plasma concentrations of MMP-9 were determined by ELISA from peripheral blood and immunohistochemistry of the same protein was carried out in formalin-fixed and paraffin wax-embedded liver specimens. The mean value of circulating concentrations of MMP-9 in healthy controls was 39.7 ng/ml (SD: +/-4.6). In NASH and HCV-infected patients, MMP-9 concentrations were higher: 69.0 ng/ml (SD: +/-14.5) and 61.7 ng/ml (SD: +/-11.0), respectively. In NASH livers, MMP-9 was mainly immunolocalized on neutrophils, whereas in HVC-infected livers it was mainly localized over biliary canaliculi, bile ducts and hepatocyte cytoplasm. The different MMP-9 immunolocalization patterns in the examined diseases suggest the presence of a different pathophysiological involvement of this protease in the fibrogenesis underlying these diseases.
    Acta histochemica 08/2009; 112(5):474-81. · 1.61 Impact Factor
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    ABSTRACT: The masking effects of antigens by chemical fixation, processing, embedding media interactions, represent a serious problem for immunohistochemical purposes. Fortunately, different approaches in antigen retrieval exist. These techniques are relatively recent and continuously expanding. This review focuses on the present state of the art in antigen retrieval methods for immunohistochemistry in light and electron microscopy. Moreover, a brief discussion on the chemical aspects of fixation, mechanism of retrieval, as well as its efficacy, is given.
    Journal of Immunological Methods 01/2009; 341(1-2):1-18. · 2.23 Impact Factor
  • F D'Amico, E Skarmoutsou
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    ABSTRACT: Gold particles labelling on ultrathin sections is extensively used for antigen localization in transmission electron microscopy. In establishing absolute or relative counts in tissue sections, it would be expedient to use stereologically based unbiased estimates for quantitative results. Nowadays, quantitative immunoelectron microscopy has achieved good and satisfactory results to test whether the gold labelling follows a non-random or a random pattern and then to draw statistical comparisons between cell subcompartments within a sample of cells or between experimental groups of cells. This brief informal review of literature focuses on the relative quantitative determinations of gold labelling of antigens as well as on the statistical distribution comparisons in transmission electron microscopy.
    Journal of Microscopy 05/2008; 230(Pt 1):9-15. · 1.63 Impact Factor
  • Fabio D'Amico, Evangelia Skarmoutsou
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    ABSTRACT: This mini-review tries to summarize the state of the art of stereological and statistical approaches used in clustering (in single immunogold labelling) and colocalization (in double immunogold labelling) studies of gold particles in transmission immunoelectron microscopy. The point pattern analysis may be useful to compare experimental pattern data to the null hypothesis of complete spatial randomness (CSR), and, furthermore to quantify the amount of clustering and/or colocalization. In particular, this paper gives an overview about the most recent literature on the subject and different approaches will be only briefly summarized.
    Micron 02/2008; 39(1):1-6. · 1.88 Impact Factor
  • Fabio D'Amico, Evangelia Skarmoutsou
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    ABSTRACT: E-cadherin and alphaE-catenin were localized in normal and chronically isoproterenol-treated acinar cells of rat parotid gland by means of immunogold labelling of Lowicryl embedded sections. Immunostaining of both experimental groups with polyclonal antibodies to E-cadherin and alphaE-catenin was mainly restricted to the areas of adherens junctions. Surprisingly, in isoproterenol-treated cell alphaE-catenin was also found on the secretory granules periphery and appeared to encircle a secretory vesicle. In isoproterenol-induced cell hyperproliferation, the maintened presence of adherens junctions components, such as E-cadherin and alphaE-catenin molecules, should be an essential prerequisite for tissue integrity. Our data suggest the presence of a correlation between the organization of actin and the localization of alphaE-catenin in the chronically isoproterenol-treated acinar cell of rat parotid gland.
    Archives of Oral Biology 03/2007; 52(2):161-7. · 1.55 Impact Factor