Elimination of neutrophils in zymosan-induced ankle inflammation by etoposide
Neutrophils play a crucial role in the pathogenesis of joint inflammatory diseases such as rheumatoid arthritis (RA). Therefore their elimination and/or a functional inhibition might have beneficial or even therapeutic effects in these diseases. In the present study we exploited the cytotoxic action...
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doaj-049c0ca241f84515955f9b036c45fbac2020-11-24T21:51:09ZengPlovdiv University Press Journal of BioScience and Biotechnology1314-62381314-62462014-12-0133183188Elimination of neutrophils in zymosan-induced ankle inflammation by etoposideViktoriya I. Milanova0Nina D. Ivanovska1Petya A. Dimitrova2Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 26, Georgi Bonchev Street, 1113 Sofia, BulgariaDepartment of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 26, Georgi Bonchev Street, 1113 Sofia, BulgariaDepartment of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 26, Georgi Bonchev Street, 1113 Sofia, BulgariaNeutrophils play a crucial role in the pathogenesis of joint inflammatory diseases such as rheumatoid arthritis (RA). Therefore their elimination and/or a functional inhibition might have beneficial or even therapeutic effects in these diseases. In the present study we exploited the cytotoxic action of etoposide to deplete neutrophils. We administrated the drug twice (at day -3 and day -1) to SCID mice having intact innate immunity and a fail in T- and B-cell maturation. Ankle inflammation was induced by the injection of zymosan (ZY). Joint damage was evaluated by histology grading system for cell infiltration and proteoglycan loss and degree of cartilage erosion. The frequencies of mature Ly6G+CD11b+ cells in bone marrow (BM) were monitored at days -4, -2 and 0 by flow cytometry. At day 7 of ankle inflammation the amounts of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-17 were measured by enzyme-linked immunosorbent assay (ELISA). Histological analysis of the joint sections showed decreased scores for cell infiltration and cartilage proteoglycan loss and reduced cartilage erosion in drug-treated zymosan injected mice in comparison to untreated group with ankle inflammation. Etoposide diminished cell numbers in BM, inhibits granulopoiesis triggered by zymosan and decreased the frequencies of mature Ly6G+CD11b+ cells in BM and eliminated Ly6G+ cells from blood and synovial fluid. We observed reduced TNF-α and impaired IL-17 production in etoposide-treated ZY group. Our data provide a proof-of principle that the elimination of neutrophils might be exploited in a design of new therapeutic approaches for joint inflammatory diseases.http://www.jbb.uni-plovdiv.bg/documents/27807/352488/jbb_2014-3(3)-pages_183-188.pdfneutrophilsetoposidezymosan-induced arthritisIL-17TNF-α |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Viktoriya I. Milanova Nina D. Ivanovska Petya A. Dimitrova |
spellingShingle |
Viktoriya I. Milanova Nina D. Ivanovska Petya A. Dimitrova Elimination of neutrophils in zymosan-induced ankle inflammation by etoposide Journal of BioScience and Biotechnology neutrophils etoposide zymosan-induced arthritis IL-17 TNF-α |
author_facet |
Viktoriya I. Milanova Nina D. Ivanovska Petya A. Dimitrova |
author_sort |
Viktoriya I. Milanova |
title |
Elimination of neutrophils in zymosan-induced ankle inflammation by etoposide |
title_short |
Elimination of neutrophils in zymosan-induced ankle inflammation by etoposide |
title_full |
Elimination of neutrophils in zymosan-induced ankle inflammation by etoposide |
title_fullStr |
Elimination of neutrophils in zymosan-induced ankle inflammation by etoposide |
title_full_unstemmed |
Elimination of neutrophils in zymosan-induced ankle inflammation by etoposide |
title_sort |
elimination of neutrophils in zymosan-induced ankle inflammation by etoposide |
publisher |
Plovdiv University Press |
series |
Journal of BioScience and Biotechnology |
issn |
1314-6238 1314-6246 |
publishDate |
2014-12-01 |
description |
Neutrophils play a crucial role in the pathogenesis of joint inflammatory diseases such as rheumatoid arthritis (RA). Therefore their elimination and/or a functional inhibition might have beneficial or even therapeutic effects in these diseases. In the present study we exploited the cytotoxic action of etoposide to deplete neutrophils. We administrated the drug twice (at day -3 and day -1) to SCID mice having intact innate immunity and a fail in T- and B-cell maturation. Ankle inflammation was induced by the injection of zymosan (ZY). Joint damage was evaluated by histology grading system for cell infiltration and proteoglycan loss and degree of cartilage erosion. The frequencies of mature Ly6G+CD11b+ cells in bone marrow (BM) were monitored at days -4, -2 and 0 by flow cytometry. At day 7 of ankle inflammation the amounts of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-17 were measured by enzyme-linked immunosorbent assay (ELISA). Histological analysis of the joint sections showed decreased scores for cell infiltration and cartilage proteoglycan loss and reduced cartilage erosion in drug-treated zymosan injected mice in comparison to untreated group with ankle inflammation. Etoposide diminished cell numbers in BM, inhibits granulopoiesis triggered by zymosan and decreased the frequencies of mature Ly6G+CD11b+ cells in BM and eliminated Ly6G+ cells from blood and synovial fluid. We observed reduced TNF-α and impaired IL-17 production in etoposide-treated ZY group. Our data provide a proof-of principle that the elimination of neutrophils might be exploited in a design of new therapeutic approaches for joint inflammatory diseases. |
topic |
neutrophils etoposide zymosan-induced arthritis IL-17 TNF-α |
url |
http://www.jbb.uni-plovdiv.bg/documents/27807/352488/jbb_2014-3(3)-pages_183-188.pdf |
work_keys_str_mv |
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