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Article ; Online: Vitamin D-binding protein and multiple sclerosis: Evidence, controversies, and needs.

Gauzzi, Maria Cristina

Multiple sclerosis (Houndmills, Basingstoke, England)

2018 Volume 24, Issue 12, Page(s) 1526–1535

Abstract: The vitamin D-binding protein (DBP) occupies a key node in the regulation of the vitamin D system. Being the main plasma carrier of vitamin D metabolites, it regulates their stability and bioavailability. However, DBP is also a multifunctional protein ... ...

Abstract	The vitamin D-binding protein (DBP) occupies a key node in the regulation of the vitamin D system. Being the main plasma carrier of vitamin D metabolites, it regulates their stability and bioavailability. However, DBP is also a multifunctional protein with roles in the organism's actin scavenging system and immunomodulation. All these activities may affect multiple sclerosis (MS) pathophysiology. DBP can be measured in blood and cerebrospinal fluid, body fluids that have been investigated as sources of accessible biomarkers of MS. Yet, available data on DBP expression and function in MS are scattered and somewhat controversial. Aims of this review are to summarize current evidence from studies on DBP in MS patients, to discuss possible shortcomings and to highlight key points that need to be addressed to gain deeper insight into the role of DBP in MS.
MeSH term(s)	Humans ; Multiple Sclerosis/metabolism ; Vitamin D-Binding Protein/metabolism
Chemical Substances	Vitamin D-Binding Protein
Language	English
Publishing date	2018-08-16
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/1352458518792433
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Article ; Online: 1,25(OH)

Sanseverino, Isabella / Rinaldi, Arturo Ottavio / Purificato, Cristina / Cortese, Antonio / Millefiorini, Enrico / Gauzzi, Maria Cristina

International journal of molecular sciences

2023 Volume 24, Issue 7

Abstract: Immune mechanisms play an essential role in driving multiple sclerosis (MS) and altered trafficking and/or activation of dendritic cells (DC) were observed in the central nervous system and cerebrospinal fluid of MS patients. Interferon β (IFNβ) has been ...

Abstract	Immune mechanisms play an essential role in driving multiple sclerosis (MS) and altered trafficking and/or activation of dendritic cells (DC) were observed in the central nervous system and cerebrospinal fluid of MS patients. Interferon β (IFNβ) has been used as a first-line therapy in MS for almost three decades and vitamin D deficiency is a recognized environmental risk factor for MS. Both IFNβ and vitamin D modulate DC functions. Here, we studied the response to 1,25-dihydoxyvitamin D3 (1,25(OH)
MeSH term(s)	Humans ; Vitamin D/pharmacology ; Vitamins/pharmacology ; Multiple Sclerosis ; Cytokines ; Chemokines
Chemical Substances	Vitamin D (1406-16-2) ; Vitamins ; Cytokines ; Chemokines
Language	English
Publishing date	2023-04-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24076717
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Article ; Online: Reply to Jakovac: COVID-19, vitamin D, and type I interferon.

Gauzzi, Maria Cristina / Fantuzzi, Laura

American journal of physiology. Endocrinology and metabolism

2020 Volume 319, Issue 2, Page(s) E245–E246

MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Interferon Type I ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2 ; Vitamin D
Chemical Substances	Interferon Type I ; Vitamin D (1406-16-2)
Keywords	covid19
Language	English
Publishing date	2020-07-16
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.00315.2020
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Article ; Online: 1,25(OH) 2 D3 Differently Modulates the Secretory Activity of IFN-DC and IL4-DC

Isabella Sanseverino / Arturo Ottavio Rinaldi / Cristina Purificato / Antonio Cortese / Enrico Millefiorini / Maria Cristina Gauzzi

International Journal of Molecular Sciences, Vol 24, Iss 6717, p

A Study in Cells from Healthy Donors and MS Patients

2023 Volume 6717

Abstract	Immune mechanisms play an essential role in driving multiple sclerosis (MS) and altered trafficking and/or activation of dendritic cells (DC) were observed in the central nervous system and cerebrospinal fluid of MS patients. Interferon β (IFNβ) has been used as a first-line therapy in MS for almost three decades and vitamin D deficiency is a recognized environmental risk factor for MS. Both IFNβ and vitamin D modulate DC functions. Here, we studied the response to 1,25-dihydoxyvitamin D3 (1,25(OH) 2 D3) of DC obtained with IFNβ/GM-CSF (IFN-DC) compared to classically derived IL4-DC, in three donor groups: MS patients free of therapy, MS patients undergoing IFNβ therapy, and healthy donors. Except for a decreased CCL2 secretion by IL4-DC from the MS group, no major defects were observed in the 1,25(OH) 2 D3 response of either IFN-DC or IL4-DC from MS donors compared to healthy donors. However, the two cell models strongly differed for vitamin D receptor level of expression as well as for basal and 1,25(OH) 2 D3-induced cytokine/chemokine secretion. 1,25(OH) 2 D3 up-modulated IL6, its soluble receptor sIL6R, and CCL5 in IL4-DC, and down-modulated IL10 in IFN-DC. IFN-DC, but not IL4-DC, constitutively secreted high levels of IL8 and of matrix-metalloproteinase-9, both down-modulated by 1,25(OH) 2 D3. DC may contribute to MS pathogenesis, but also provide an avenue for therapeutic intervention. 1,25(OH) 2 D3-induced tolerogenic DC are in clinical trial for MS. We show that the protocol of in vitro DC differentiation qualitatively and quantitatively affects secretion of cytokines and chemokines deeply involved in MS pathogenesis.
Keywords	type I IFN ; vitamin D ; chemokine ; cytokine ; monocyte-derived dendritic cell ; multiple sclerosis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Reply to Jakovac: COVID-19, vitamin D, and type I interferon

Gauzzi, Maria Cristina / Fantuzzi, Laura

Am J Physiol Endocrinol Metab

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #647400
Database	COVID19

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Article ; Online: Dual CCR5/CCR2 targeting: opportunities for the cure of complex disorders.

Fantuzzi, Laura / Tagliamonte, Maria / Gauzzi, Maria Cristina / Lopalco, Lucia

Cellular and molecular life sciences : CMLS

2019 Volume 76, Issue 24, Page(s) 4869–4886

Abstract: The chemokine system mediates acute inflammation by driving leukocyte migration to damaged or infected tissues. However, elevated expression of chemokines and their receptors can contribute to chronic inflammation and malignancy. Thus, great effort has ... ...

Abstract	The chemokine system mediates acute inflammation by driving leukocyte migration to damaged or infected tissues. However, elevated expression of chemokines and their receptors can contribute to chronic inflammation and malignancy. Thus, great effort has been taken to target these molecules. The first hint of the druggability of the chemokine system was derived from the role of chemokine receptors in HIV infection. CCR5 and CXCR4 function as essential co-receptors for HIV entry, with the former accounting for most new HIV infections worldwide. Not by chance, an anti-CCR5 compound, maraviroc, was the first FDA-approved chemokine receptor-targeting drug. CCR5, by directing leukocytes to sites of inflammation and regulating their activation, also represents an important player in the inflammatory response. This function is shared with CCR2 and its selective ligand CCL2, which constitute the primary chemokine axis driving the recruitment of monocytes/macrophages to inflammatory sites. Both receptors are indeed involved in the pathogenesis of several immune-mediated diseases, and dual CCR5/CCR2 targeting is emerging as a more efficacious strategy than targeting either receptor alone in the treatment of complex human disorders. In this review, we focus on the distinctive and complementary contributions of CCR5 and CCR2/CCL2 in HIV infection, multiple sclerosis, liver fibrosis and associated hepatocellular carcinoma. The emerging therapeutic approaches based on the inhibition of these chemokine axes are highlighted.
MeSH term(s)	Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/therapy ; Chemokine CCL2/genetics ; Gene Targeting ; HIV/genetics ; HIV/pathogenicity ; HIV Infections/genetics ; HIV Infections/therapy ; HIV Infections/virology ; Humans ; Inflammation/genetics ; Inflammation/therapy ; Liver Cirrhosis/genetics ; Liver Cirrhosis/therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/therapy ; Multiple Sclerosis/genetics ; Multiple Sclerosis/therapy ; Receptors, CCR2/genetics ; Receptors, CCR5/genetics
Chemical Substances	CCL2 protein, human ; CCR2 protein, human ; CCR5 protein, human ; Chemokine CCL2 ; Receptors, CCR2 ; Receptors, CCR5
Language	English
Publishing date	2019-08-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-019-03255-6
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Zs.A 195: Show issues

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Article ; Online: Understanding the regulation of APOBEC3 expression: Current evidence and much to learn.

Covino, Daniela Angela / Gauzzi, Maria Cristina / Fantuzzi, Laura

Journal of leukocyte biology

2017 Volume 103, Issue 3, Page(s) 433–444

Abstract: The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of cytosine deaminases plays crucial roles in innate immunity through the ability of restricting viral replication by deamination and mutation of viral genomes. The ... ...

Abstract	The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of cytosine deaminases plays crucial roles in innate immunity through the ability of restricting viral replication by deamination and mutation of viral genomes. The antiviral function of these proteins was first discovered when research in the field of HIV infection revealed that one member of the family, namely APOBEC3G, restricts HIV infection in T lymphocytes and that the viral infectivity factor protein drives the proteosomal degradation of this enzyme, thus overriding its antiviral function. Recent advances in cancer genomics, together with biochemical characterization of the APOBEC3 enzymes, have now implicated some family members in somatic mutagenesis during carcinogenesis. While several studies investigated the downstream consequences of APOBEC3 expression and activity, either in the context of viral infection or tumorigenesis, little is known on the upstream mechanisms regulating APOBEC3 expression. Such knowledge would be of huge importance in developing innovative approaches to strengthen antiviral innate immunity on one side and to prevent cancer development on the other. This mini review summarizes research advances on the molecular mechanisms regulating the expression of APOBEC3 family members in selected immune cell populations and cancer cells.
MeSH term(s)	APOBEC-3G Deaminase/genetics ; APOBEC-3G Deaminase/metabolism ; Animals ; Gene Expression Regulation, Neoplastic ; Humans ; Immunity, Innate/immunology ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/pathology
Chemical Substances	APOBEC-3G Deaminase (EC 3.5.4.5) ; APOBEC3G protein, human (EC 3.5.4.5)
Language	English
Publishing date	2017-12-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1002/JLB.2MR0717-310R
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Zs.A 603: Show issues

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Article ; Online: Transcriptome Profiling of Human Monocyte-Derived Macrophages Upon CCL2 Neutralization Reveals an Association Between Activation of Innate Immune Pathways and Restriction of HIV-1 Gene Expression.

Covino, Daniela Angela / Kaczor-Urbanowicz, Karolina Elżbieta / Lu, Jing / Chiantore, Maria Vincenza / Fiorucci, Gianna / Vescio, Maria Fenicia / Catapano, Laura / Purificato, Cristina / Galluzzo, Clementina Maria / Amici, Roberta / Andreotti, Mauro / Gauzzi, Maria Cristina / Pellegrini, Matteo / Fantuzzi, Laura

Frontiers in immunology

2020 Volume 11, Page(s) 2129

Abstract: Macrophages are key targets of human immunodeficiency virus type 1 (HIV-1) infection and main producers of the proinflammatory chemokine CC chemokine ligand 2 (CCL2), whose expression is induced by HIV-1 ... ...

Abstract	Macrophages are key targets of human immunodeficiency virus type 1 (HIV-1) infection and main producers of the proinflammatory chemokine CC chemokine ligand 2 (CCL2), whose expression is induced by HIV-1 both
MeSH term(s)	Antibodies, Neutralizing/immunology ; Antibodies, Neutralizing/pharmacology ; Antibody Specificity ; Cells, Cultured ; Chemokine CCL2/antagonists & inhibitors ; Chemokine CCL2/immunology ; Chemokine CCL2/pharmacology ; Cytidine Deaminase/physiology ; Datasets as Topic ; Gene Expression Profiling ; Gene Expression Regulation, Viral/drug effects ; HIV-1/genetics ; Humans ; Immunity, Innate ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/metabolism ; Macrophages/virology ; MicroRNAs/biosynthesis ; MicroRNAs/genetics ; Molecular Sequence Annotation ; NF-kappa B/metabolism ; Proteins/physiology ; RNA, Viral/biosynthesis ; RNA, Viral/genetics ; RNA-Seq ; Real-Time Polymerase Chain Reaction ; Virus Latency ; Virus Replication
Chemical Substances	Antibodies, Neutralizing ; CCL2 protein, human ; Chemokine CCL2 ; MIRN155 microRNA, human ; MicroRNAs ; NF-kappa B ; Proteins ; RNA, Viral ; APOBEC3A protein, human (EC 3.5.4.5) ; Cytidine Deaminase (EC 3.5.4.5)
Language	English
Publishing date	2020-09-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.02129
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Article ; Online: Dual requirement for STAT signaling in dendritic cell immunobiology.

Donninelli, Gloria / Sanseverino, Isabella / Purificato, Cristina / Gessani, Sandra / Gauzzi, Maria Cristina

Immunobiology

2017 Volume 223, Issue 3, Page(s) 342–347

Abstract: Dendritic cells (DC) represent an attractive target for therapeutic manipulation of the immune system and enhancement of insufficient immune response in cancer. STAT family members play key roles in the differentiation and activation of DC, a feature ... ...

Abstract	Dendritic cells (DC) represent an attractive target for therapeutic manipulation of the immune system and enhancement of insufficient immune response in cancer. STAT family members play key roles in the differentiation and activation of DC, a feature that is currently being exploited in DC-based therapies. We previously reported that the small-molecule Stattic, originally developed as a STAT3-specific inhibitor, also inhibits STAT1 and STAT2 phosphorylation in DC exposed to cytokines or LPS. Aim of this study was to investigate the functional consequences of in vitro treatment with Stattic on DC immunobiology. Interestingly, we observed an opposite effect of Stattic on DC immunophenotype depending on the activation state. While the expression of costimulatory, coinhibitory, MHC class II and CD83 molecules was enhanced in immature DC exposed to Stattic, the LPS induced up-modulation of these molecules was strongly repressed. An effective blockade of LPS-induced secretion of proinflammatory cytokines and capacity to stimulate a Th1 polarization was also observed in the presence of Stattic. Our results indicate that the immunological consequences of STAT inhibition in DC vary depending on the cell activation state. This knowledge is of relevance for anticipating potential effects of STAT-targeted therapeutics, and pursuing selective DC manipulation in clinical applications.
MeSH term(s)	Anti-Inflammatory Agents/pharmacology ; Antigens, CD/metabolism ; Cell Differentiation/drug effects ; Cells, Cultured ; Cyclic S-Oxides/pharmacology ; Cytokines/metabolism ; Dendritic Cells/immunology ; Humans ; Immunoglobulins/metabolism ; Immunophenotyping ; Lipopolysaccharides/immunology ; Lymphocyte Activation ; Membrane Glycoproteins/metabolism ; Neoplasms/drug therapy ; Phosphorylation ; STAT3 Transcription Factor/antagonists & inhibitors ; Signal Transduction ; Small Molecule Libraries ; T-Lymphocytes/immunology ; CD83 Antigen
Chemical Substances	Anti-Inflammatory Agents ; Antigens, CD ; Cyclic S-Oxides ; Cytokines ; Immunoglobulins ; Lipopolysaccharides ; Membrane Glycoproteins ; STAT3 Transcription Factor ; Small Molecule Libraries ; stattic
Language	English
Publishing date	2017-10-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	563292-4
ISSN	1878-3279 ; 0171-2985
ISSN (online)	1878-3279
ISSN	0171-2985
DOI	10.1016/j.imbio.2017.10.049
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Article: Dual CCR5/CCR2 targeting: opportunities for the cure of complex disorders

Fantuzzi, Laura / Tagliamonte, Maria / Gauzzi, Maria Cristina / Lopalco, Lucia

Cellular and molecular life sciences. 2019 Dec., v. 76, no. 24

2019

Abstract	The chemokine system mediates acute inflammation by driving leukocyte migration to damaged or infected tissues. However, elevated expression of chemokines and their receptors can contribute to chronic inflammation and malignancy. Thus, great effort has been taken to target these molecules. The first hint of the druggability of the chemokine system was derived from the role of chemokine receptors in HIV infection. CCR5 and CXCR4 function as essential co-receptors for HIV entry, with the former accounting for most new HIV infections worldwide. Not by chance, an anti-CCR5 compound, maraviroc, was the first FDA-approved chemokine receptor-targeting drug. CCR5, by directing leukocytes to sites of inflammation and regulating their activation, also represents an important player in the inflammatory response. This function is shared with CCR2 and its selective ligand CCL2, which constitute the primary chemokine axis driving the recruitment of monocytes/macrophages to inflammatory sites. Both receptors are indeed involved in the pathogenesis of several immune-mediated diseases, and dual CCR5/CCR2 targeting is emerging as a more efficacious strategy than targeting either receptor alone in the treatment of complex human disorders. In this review, we focus on the distinctive and complementary contributions of CCR5 and CCR2/CCL2 in HIV infection, multiple sclerosis, liver fibrosis and associated hepatocellular carcinoma. The emerging therapeutic approaches based on the inhibition of these chemokine axes are highlighted.
Keywords	HIV infections ; cell movement ; drugs ; hepatoma ; humans ; inflammation ; ligands ; liver cirrhosis ; macrophages ; monocytes ; pathogenesis ; sclerosis ; therapeutics
Language	English
Dates of publication	2019-12
Size	p. 4869-4886.
Publishing place	Springer International Publishing
Document type	Article
Note	NAL-AP-2-clean ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-019-03255-6
Database	NAL-Catalogue (AGRICOLA)

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