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Specific effect of immunomodulatory quinoline-3-carboxamide ABR-215757 in GM-CSF stimulated bone marrow cell cultures: Block of initiation of proliferation of Gr-1(+) cells.

Helmersson, Sofia LU ; Stenström, Martin LU ; Leanderson, Tomas LU and Ivars, Fredrik LU (2011) In International Immunopharmacology 11. p.1045-1051
Abstract
Quinoline-3-carboxamides are currently in clinical development for treatment of both autoimmune disease and cancer. Carboxamides such as ABR-215757 (5757) have shown efficacy in several in vivo mouse models of human inflammatory autoimmune disease. Some microbial infections in mice cause GM-CSF dependent accumulation of dendritic cells expressing TNFα and inducible nitric oxide synthase (iNOS; Tip-DCs) in lymphoid organs. Functionally similar DCs develop in GM-CSF stimulated bone marrow (BM) cell cultures and offered an in vitro model that allowed us to study the impact of 5757 on cellular development of relevance for in vivo inflammatory conditions. We show in here that addition of 5757 to such cultures, in a dose-dependent way increased... (More)
Quinoline-3-carboxamides are currently in clinical development for treatment of both autoimmune disease and cancer. Carboxamides such as ABR-215757 (5757) have shown efficacy in several in vivo mouse models of human inflammatory autoimmune disease. Some microbial infections in mice cause GM-CSF dependent accumulation of dendritic cells expressing TNFα and inducible nitric oxide synthase (iNOS; Tip-DCs) in lymphoid organs. Functionally similar DCs develop in GM-CSF stimulated bone marrow (BM) cell cultures and offered an in vitro model that allowed us to study the impact of 5757 on cellular development of relevance for in vivo inflammatory conditions. We show in here that addition of 5757 to such cultures, in a dose-dependent way increased the frequency of DCs, while it reduced the frequency of Gr-1(+) cells by inhibiting their proliferation. This effect was specific as the compound neither influenced DC development from myeloid progenitors, nor the development of granulocytes in G-CSF stimulated BM cell cultures. Importantly, we also show that 5757 treatment reduced the accumulation of Gr-1(+) cells during inflammation in vivo. We therefore propose that this compound may ameliorate autoimmune disease by blocking proliferation of Gr-1(+) cells during inflammation-induced mobilization of myeloid cells. (Less)
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type
Contribution to journal
publication status
published
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in
International Immunopharmacology
volume
11
pages
1045 - 1051
publisher
Elsevier
external identifiers
  • wos:000293723400021
  • pmid:21388612
  • scopus:84860404211
ISSN
1878-1705
DOI
10.1016/j.intimp.2011.02.025
language
English
LU publication?
yes
id
15d790d5-25e2-4deb-a706-47596f5a1ec1 (old id 1884159)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21388612?dopt=Abstract
date added to LUP
2011-04-01 14:57:20
date last changed
2017-01-01 03:17:03
@article{15d790d5-25e2-4deb-a706-47596f5a1ec1,
  abstract     = {Quinoline-3-carboxamides are currently in clinical development for treatment of both autoimmune disease and cancer. Carboxamides such as ABR-215757 (5757) have shown efficacy in several in vivo mouse models of human inflammatory autoimmune disease. Some microbial infections in mice cause GM-CSF dependent accumulation of dendritic cells expressing TNFα and inducible nitric oxide synthase (iNOS; Tip-DCs) in lymphoid organs. Functionally similar DCs develop in GM-CSF stimulated bone marrow (BM) cell cultures and offered an in vitro model that allowed us to study the impact of 5757 on cellular development of relevance for in vivo inflammatory conditions. We show in here that addition of 5757 to such cultures, in a dose-dependent way increased the frequency of DCs, while it reduced the frequency of Gr-1(+) cells by inhibiting their proliferation. This effect was specific as the compound neither influenced DC development from myeloid progenitors, nor the development of granulocytes in G-CSF stimulated BM cell cultures. Importantly, we also show that 5757 treatment reduced the accumulation of Gr-1(+) cells during inflammation in vivo. We therefore propose that this compound may ameliorate autoimmune disease by blocking proliferation of Gr-1(+) cells during inflammation-induced mobilization of myeloid cells.},
  author       = {Helmersson, Sofia and Stenström, Martin and Leanderson, Tomas and Ivars, Fredrik},
  issn         = {1878-1705},
  language     = {eng},
  pages        = {1045--1051},
  publisher    = {Elsevier},
  series       = {International Immunopharmacology},
  title        = {Specific effect of immunomodulatory quinoline-3-carboxamide ABR-215757 in GM-CSF stimulated bone marrow cell cultures: Block of initiation of proliferation of Gr-1(+) cells.},
  url          = {http://dx.doi.org/10.1016/j.intimp.2011.02.025},
  volume       = {11},
  year         = {2011},
}