Serum DNase I, soluble Fas/FasL levels and cell surface Fas expression in patients with SLE: A possible explanation for the lack of efficacy of hrDNase I treatment

Elisa Tinazzii, Antonio Puccetti, Roberto Gerli, Antonella Rigo, Paola Migliorini, Sara Simeoni, Ruggero Beri, Marzia Dolcino, Nicola Martinelli, Roberto Corrocher, Claudio Lunardi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The objectives of the study are to evaluate DNase I serum levels and their correlation with soluble Fas (sFas) and soluble Fas ligand (sFasL) and with cell surface Fas expression in patients with systemic lupus erythematosus (SLE), thus contributing to the dysregulated apoptosis typical of the disease. The methods include the following: Serum DNase I levels in patients and in controls were detected using the dot blot method and quantified by densitometry; sFas and sFasL were quantified using an ELISA system. Cell surface Fas expression was evaluated by FACS analysis. Apoptosis was studied by means of internucleosomal DNA degradation using a commercially available kit. The results are as follows: We found a significant difference in DNase I, sFas and sFasL serum levels between patients and controls. Levels of DNase I 1 are more represented in patients with SLE. Active SLE is strongly associated with high sFas levels and detectable sFasL. DNase I does not correlate with sFas or sFasL, whereas it correlates with T cell surface Fas expression that is higher in patients with active SLE than in healthy controls. Finally, administration of exogenous human recombinant DNase (hrDNase) I to freshly isolated T cells up-regulates cell surface Fas expression and induces increased susceptibility to Fas-mediated apoptosis. In conclusion, our findings confirm that DNase I is low in SLE and suggest that it may play a role in apoptosis in SLE by regulating the surface expression of the cell death molecule Fas. This role may contribute to explain the inefficacy of hrDNase I in SLE, a treatment proposed for the ability of DNase I to remove DNA from auto-antigenic nucleoprotein complexes.

Original languageEnglish
Pages (from-to)237-243
Number of pages7
JournalInternational Immunology
Volume21
Issue number3
DOIs
Publication statusPublished - 2009

Fingerprint

Deoxyribonuclease I
Systemic Lupus Erythematosus
Fas Ligand Protein
Serum
Apoptosis
Therapeutics
T-Lymphocytes
Nucleoproteins
Densitometry
DNA
Cell Death
Up-Regulation
Enzyme-Linked Immunosorbent Assay

Keywords

  • DNase I
  • Human recombinant DNase I
  • SLE
  • Soluble Fas/FasL

ASJC Scopus subject areas

  • Immunology

Cite this

Serum DNase I, soluble Fas/FasL levels and cell surface Fas expression in patients with SLE : A possible explanation for the lack of efficacy of hrDNase I treatment. / Tinazzii, Elisa; Puccetti, Antonio; Gerli, Roberto; Rigo, Antonella; Migliorini, Paola; Simeoni, Sara; Beri, Ruggero; Dolcino, Marzia; Martinelli, Nicola; Corrocher, Roberto; Lunardi, Claudio.

In: International Immunology, Vol. 21, No. 3, 2009, p. 237-243.

Research output: Contribution to journalArticle

Tinazzii, E, Puccetti, A, Gerli, R, Rigo, A, Migliorini, P, Simeoni, S, Beri, R, Dolcino, M, Martinelli, N, Corrocher, R & Lunardi, C 2009, 'Serum DNase I, soluble Fas/FasL levels and cell surface Fas expression in patients with SLE: A possible explanation for the lack of efficacy of hrDNase I treatment', International Immunology, vol. 21, no. 3, pp. 237-243. https://doi.org/10.1093/intimm/dxn142
Tinazzii, Elisa ; Puccetti, Antonio ; Gerli, Roberto ; Rigo, Antonella ; Migliorini, Paola ; Simeoni, Sara ; Beri, Ruggero ; Dolcino, Marzia ; Martinelli, Nicola ; Corrocher, Roberto ; Lunardi, Claudio. / Serum DNase I, soluble Fas/FasL levels and cell surface Fas expression in patients with SLE : A possible explanation for the lack of efficacy of hrDNase I treatment. In: International Immunology. 2009 ; Vol. 21, No. 3. pp. 237-243.
@article{88b599bc7d08446191f4059f8afb2b6c,
title = "Serum DNase I, soluble Fas/FasL levels and cell surface Fas expression in patients with SLE: A possible explanation for the lack of efficacy of hrDNase I treatment",
abstract = "The objectives of the study are to evaluate DNase I serum levels and their correlation with soluble Fas (sFas) and soluble Fas ligand (sFasL) and with cell surface Fas expression in patients with systemic lupus erythematosus (SLE), thus contributing to the dysregulated apoptosis typical of the disease. The methods include the following: Serum DNase I levels in patients and in controls were detected using the dot blot method and quantified by densitometry; sFas and sFasL were quantified using an ELISA system. Cell surface Fas expression was evaluated by FACS analysis. Apoptosis was studied by means of internucleosomal DNA degradation using a commercially available kit. The results are as follows: We found a significant difference in DNase I, sFas and sFasL serum levels between patients and controls. Levels of DNase I 1 are more represented in patients with SLE. Active SLE is strongly associated with high sFas levels and detectable sFasL. DNase I does not correlate with sFas or sFasL, whereas it correlates with T cell surface Fas expression that is higher in patients with active SLE than in healthy controls. Finally, administration of exogenous human recombinant DNase (hrDNase) I to freshly isolated T cells up-regulates cell surface Fas expression and induces increased susceptibility to Fas-mediated apoptosis. In conclusion, our findings confirm that DNase I is low in SLE and suggest that it may play a role in apoptosis in SLE by regulating the surface expression of the cell death molecule Fas. This role may contribute to explain the inefficacy of hrDNase I in SLE, a treatment proposed for the ability of DNase I to remove DNA from auto-antigenic nucleoprotein complexes.",
keywords = "DNase I, Human recombinant DNase I, SLE, Soluble Fas/FasL",
author = "Elisa Tinazzii and Antonio Puccetti and Roberto Gerli and Antonella Rigo and Paola Migliorini and Sara Simeoni and Ruggero Beri and Marzia Dolcino and Nicola Martinelli and Roberto Corrocher and Claudio Lunardi",
year = "2009",
doi = "10.1093/intimm/dxn142",
language = "English",
volume = "21",
pages = "237--243",
journal = "International Immunology",
issn = "0953-8178",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Serum DNase I, soluble Fas/FasL levels and cell surface Fas expression in patients with SLE

T2 - A possible explanation for the lack of efficacy of hrDNase I treatment

AU - Tinazzii, Elisa

AU - Puccetti, Antonio

AU - Gerli, Roberto

AU - Rigo, Antonella

AU - Migliorini, Paola

AU - Simeoni, Sara

AU - Beri, Ruggero

AU - Dolcino, Marzia

AU - Martinelli, Nicola

AU - Corrocher, Roberto

AU - Lunardi, Claudio

PY - 2009

Y1 - 2009

N2 - The objectives of the study are to evaluate DNase I serum levels and their correlation with soluble Fas (sFas) and soluble Fas ligand (sFasL) and with cell surface Fas expression in patients with systemic lupus erythematosus (SLE), thus contributing to the dysregulated apoptosis typical of the disease. The methods include the following: Serum DNase I levels in patients and in controls were detected using the dot blot method and quantified by densitometry; sFas and sFasL were quantified using an ELISA system. Cell surface Fas expression was evaluated by FACS analysis. Apoptosis was studied by means of internucleosomal DNA degradation using a commercially available kit. The results are as follows: We found a significant difference in DNase I, sFas and sFasL serum levels between patients and controls. Levels of DNase I 1 are more represented in patients with SLE. Active SLE is strongly associated with high sFas levels and detectable sFasL. DNase I does not correlate with sFas or sFasL, whereas it correlates with T cell surface Fas expression that is higher in patients with active SLE than in healthy controls. Finally, administration of exogenous human recombinant DNase (hrDNase) I to freshly isolated T cells up-regulates cell surface Fas expression and induces increased susceptibility to Fas-mediated apoptosis. In conclusion, our findings confirm that DNase I is low in SLE and suggest that it may play a role in apoptosis in SLE by regulating the surface expression of the cell death molecule Fas. This role may contribute to explain the inefficacy of hrDNase I in SLE, a treatment proposed for the ability of DNase I to remove DNA from auto-antigenic nucleoprotein complexes.

AB - The objectives of the study are to evaluate DNase I serum levels and their correlation with soluble Fas (sFas) and soluble Fas ligand (sFasL) and with cell surface Fas expression in patients with systemic lupus erythematosus (SLE), thus contributing to the dysregulated apoptosis typical of the disease. The methods include the following: Serum DNase I levels in patients and in controls were detected using the dot blot method and quantified by densitometry; sFas and sFasL were quantified using an ELISA system. Cell surface Fas expression was evaluated by FACS analysis. Apoptosis was studied by means of internucleosomal DNA degradation using a commercially available kit. The results are as follows: We found a significant difference in DNase I, sFas and sFasL serum levels between patients and controls. Levels of DNase I 1 are more represented in patients with SLE. Active SLE is strongly associated with high sFas levels and detectable sFasL. DNase I does not correlate with sFas or sFasL, whereas it correlates with T cell surface Fas expression that is higher in patients with active SLE than in healthy controls. Finally, administration of exogenous human recombinant DNase (hrDNase) I to freshly isolated T cells up-regulates cell surface Fas expression and induces increased susceptibility to Fas-mediated apoptosis. In conclusion, our findings confirm that DNase I is low in SLE and suggest that it may play a role in apoptosis in SLE by regulating the surface expression of the cell death molecule Fas. This role may contribute to explain the inefficacy of hrDNase I in SLE, a treatment proposed for the ability of DNase I to remove DNA from auto-antigenic nucleoprotein complexes.

KW - DNase I

KW - Human recombinant DNase I

KW - SLE

KW - Soluble Fas/FasL

UR - http://www.scopus.com/inward/record.url?scp=61349098038&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61349098038&partnerID=8YFLogxK

U2 - 10.1093/intimm/dxn142

DO - 10.1093/intimm/dxn142

M3 - Article

C2 - 19181929

AN - SCOPUS:61349098038

VL - 21

SP - 237

EP - 243

JO - International Immunology

JF - International Immunology

SN - 0953-8178

IS - 3

ER -