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Inflammation Research

, Volume 66, Issue 12, pp 1107–1116 | Cite as

SERPING1 mRNA overexpression in monocytes from HIV+ patients

  • C. Sanfilippo
  • D. Cambria
  • A. Longo
  • M. Palumbo
  • R. Avola
  • M. Pinzone
  • G. Nunnari
  • F. Condorelli
  • G. Musumeci
  • R. Imbesi
  • P. Castogiovanni
  • L. Malaguarnera
  • Michelino Di Rosa
Original Research Paper

Abstract

Objective

The HIV-1 virus activates the complement system, an essential element of the immune system. SERPING1 is a protease inhibitor that disables C1r/C1s in the C1 complex of the classical complement pathway.

Methods

In this paper, we performed an analysis of several microarrays deposited in GEO dataset to demonstrate that SERPING1 mRNA is modulated in CD14+ monocytes from HIV-1-infected individuals. In addition, data were validated on monocytes isolated from seronegative healthy volunteers, treated with IFNs.

Results

Our analysis shows that SERPING1 mRNA is overexpressed in monocytes from HIV-1+ patients and the expression levels correlate positively with viral load and negatively with the CD4+ T-cell count. Of note, anti-retroviral therapy is able to reduce the levels of SERPING1 mRNA, ex vivo. In addition, we found that 30% of the SERPING1 genes network is upregulated in monocytes from HIV-1+ patients. Noteworthy, the expression levels of IFITM1—an antiviral molecule belonging to the genes network—correlate positively with SERPING1 expression. Interestingly, the monocytes treatment with IFN-gamma, IFN-beta and IFN-alpha significantly upregulates the SERPING1 mRNA expression levels.

Conclusions

From the outcome of our investigation, it is possible to conclude that SERPING1 and its network serve as important components of the innate immune system to restrict HIV-1 infection.

Keywords

SERPING1 C1-INH Monocyte Complement HIV-1 IFN-gamma 

Abbreviations

LVL

Low viral load

HVL

High viral load

HIV-1

Human immunodeficiency virus 1

IFNγ

Interferon-gamma

IFNα

Interferon-alpha

IFNβ

Interferon-beta

AHI

Acute human immunodeficiency virus (HIV) infection

C1-INH or SERPING1

C1 inhibitor

TCID50

50% Tissue culture infective dose

IFITM1

Interferon-induced transmembrane protein 1

HAART

Highly active anti-retroviral therapy

C4d

Complement component 4 fragment d

HAE

Type I and II hereditary angioedema

PVL

Plasma viral load

AP

Acute phase

PBMCs

Human peripheral blood mononuclear cells

BVL

Blood viral load

Notes

Acknowledgements

We would also like to show our gratitude to the authors of microarray dataset (GSE18464, GSE5220, GSE13395 and GSE25669) made available on line, for consultation and re-analysis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Supplementary material

11_2017_1091_MOESM1_ESM.tif (1.2 mb)
Supplementary Fig. 1: SERPING1 gene network constellation. The STRING network on 15 common genes to the HVL vs seronegative Healthy donors upregulated genes. The genes shown in red (58%) belong to the IFNs type I pathways (TIFF 1200 kb)
11_2017_1091_MOESM2_ESM.tif (40 kb)
Supplementary Fig. 2: SERPING1 levels correlate with IFNs gene family expression. The comparison analysis of the two sub-groups (> 85th and < 15th percentile of SERPING1 expression levels) have restituted 6002 significant modulated genes. The most significant genes belonged to the Interferon Family Genes (IFI44, IRF7, IFI44L, IFIT1, IFIT3, IFIT2, IFIH1, IFITM3 and IFITM1). P values < 0.05 were considered to be statistically significant (*p < 0.05; **p < 0.005;***p < 0.0005; ****p < 0.00005 and ns, not significant) (TIFF 39 kb)
11_2017_1091_MOESM3_ESM.tif (113 kb)
Supplementary Fig. 3: HIV-1 virus effect on SERPING1 mRNA expression levels in Peripheral blood lymphocytes. The HIV-1 virus not modulated SERPING1 expression levels (GSE13395) (A). The analysis of different leukocyte populations (GSE25669) showed that SERPING1 expression levels was significantly upregulated (p = 0.016) only in monocytes of HIV-1 patients compared to monocytes of seronegative healthy donors (B). Results are expressed as Log2 intensity expression levels and presented as bars (one bar per column) and mean ± SD. P values < 0.05 were considered to be statistically significant (*p < 0.05; **p < 0.005;***p < 0.0005; ****p < 0.00005 and ns, not significant) (TIFF 113 kb)
11_2017_1091_MOESM4_ESM.xlsx (13 kb)
Supplementary Table 1: The Genes Ontology. Complete list of functions obtained during the GIANT and PHANTER analysis (XLSX 12 kb)
11_2017_1091_MOESM5_ESM.xlsx (4.3 mb)
Supplementary Table 2: GSE18464 dataset centered on SERPING1 expression levels. Complete list of statistically significant genes obtained by the comparison analysis of the two sub-groups, high and low SERPING1 expression levels (XLSX 4375 kb)

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • C. Sanfilippo
    • 1
  • D. Cambria
    • 1
  • A. Longo
    • 1
  • M. Palumbo
    • 1
  • R. Avola
    • 1
  • M. Pinzone
    • 2
  • G. Nunnari
    • 3
  • F. Condorelli
    • 4
  • G. Musumeci
    • 5
  • R. Imbesi
    • 5
  • P. Castogiovanni
    • 5
  • L. Malaguarnera
    • 1
  • Michelino Di Rosa
    • 1
    • 5
  1. 1.Department of Biomedical and Biotechnological SciencesUniversity of CataniaCataniaItaly
  2. 2.Department of Pathology and Laboratory Medicine, School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Unit of Infectious Diseases, Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly
  4. 4.Department of Pharmacological SciencesUniversità del Piemonte Orientale “A. Avogadro”NovaraItaly
  5. 5.Human Anatomy and Histology Section, Department of Biomedical and Biotechnological Sciences, School of MedicineUniversity of CataniaCataniaItaly

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