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Macrophage Responses to Interferon-gamma are Dependent on Cystatin C Levels.

Frendéus, Katarina H; Wallin, Hanna LU ; Janciauskiene, Sabina LU and Abrahamson, Magnus LU (2009) In International Journal of Biochemistry and Cell Biology 41. p.2262-2269
Abstract
The aim of the present investigation was to elucidate possible effects of cystatin C on inflammatory responses mediated by macrophages. Previously it has been shown that in vitro treatment of murine peritoneal macrophages with interferon-gamma (IFN-gamma) causes a down-regulation of cystatin C secretion. To investigate whether such changes in cystatin C expression in turn can affect inflammatory responses mediated by macrophages, we have compared effects of IFN-gamma on macrophages isolated from wild-type (cysC(+/+)) and cystatin C knockout (cysC(-/-)) mice. It was shown that IFN-gamma-primed cysC(-/-) macrophages exhibit significantly higher interleukin-10 (IL-10) but lower tumor necrosis factor-alpha (TNF-alpha) expression, and reduced... (More)
The aim of the present investigation was to elucidate possible effects of cystatin C on inflammatory responses mediated by macrophages. Previously it has been shown that in vitro treatment of murine peritoneal macrophages with interferon-gamma (IFN-gamma) causes a down-regulation of cystatin C secretion. To investigate whether such changes in cystatin C expression in turn can affect inflammatory responses mediated by macrophages, we have compared effects of IFN-gamma on macrophages isolated from wild-type (cysC(+/+)) and cystatin C knockout (cysC(-/-)) mice. It was shown that IFN-gamma-primed cysC(-/-) macrophages exhibit significantly higher interleukin-10 (IL-10) but lower tumor necrosis factor-alpha (TNF-alpha) expression, and reduced nuclear factor (NF)-kappaB p65 activation, compared to similarily primed cysC(+/+) cells. Exogenously added cystatin C enhanced IFN-gamma-induced activation of NF-kappaB p65 and increased mRNA levels for inducible NO synthase (iNOS) in cysC(-/-) macrophages as well as levels of nitric oxide and TNF-alpha in the cell culture medium, in agreement with an enhanced pro-inflammatory response. Accordingly, IFN-gamma-induced IL-10 mRNA expression in cysC(-/-) macrophages was down-regulated by exogenously added cystatin C square. Taken together, our data provide evidence that changes in cystatin C levels alter macrophage responses to IFN-gamma. The latter downregulates the production of cystatin C, which leads to a suppressed inflammatory condition with enhanced IL-10 levels and downregulated TNF-alpha and NF-kappaB. It is concluded that cystatin C through this effect can act as an immunomodulatory molecule. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
International Journal of Biochemistry and Cell Biology
volume
41
pages
2262 - 2269
publisher
Elsevier
external identifiers
  • WOS:000271124700022
  • PMID:19446036
  • Scopus:70349283018
ISSN
1878-5875
DOI
10.1016/j.biocel.2009.05.005
language
English
LU publication?
yes
id
de01cc68-06fb-4757-8a39-4bcc944362ce (old id 1412253)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19446036?dopt=Abstract
date added to LUP
2009-06-03 12:47:16
date last changed
2016-11-10 14:29:33
@misc{de01cc68-06fb-4757-8a39-4bcc944362ce,
  abstract     = {The aim of the present investigation was to elucidate possible effects of cystatin C on inflammatory responses mediated by macrophages. Previously it has been shown that in vitro treatment of murine peritoneal macrophages with interferon-gamma (IFN-gamma) causes a down-regulation of cystatin C secretion. To investigate whether such changes in cystatin C expression in turn can affect inflammatory responses mediated by macrophages, we have compared effects of IFN-gamma on macrophages isolated from wild-type (cysC(+/+)) and cystatin C knockout (cysC(-/-)) mice. It was shown that IFN-gamma-primed cysC(-/-) macrophages exhibit significantly higher interleukin-10 (IL-10) but lower tumor necrosis factor-alpha (TNF-alpha) expression, and reduced nuclear factor (NF)-kappaB p65 activation, compared to similarily primed cysC(+/+) cells. Exogenously added cystatin C enhanced IFN-gamma-induced activation of NF-kappaB p65 and increased mRNA levels for inducible NO synthase (iNOS) in cysC(-/-) macrophages as well as levels of nitric oxide and TNF-alpha in the cell culture medium, in agreement with an enhanced pro-inflammatory response. Accordingly, IFN-gamma-induced IL-10 mRNA expression in cysC(-/-) macrophages was down-regulated by exogenously added cystatin C square. Taken together, our data provide evidence that changes in cystatin C levels alter macrophage responses to IFN-gamma. The latter downregulates the production of cystatin C, which leads to a suppressed inflammatory condition with enhanced IL-10 levels and downregulated TNF-alpha and NF-kappaB. It is concluded that cystatin C through this effect can act as an immunomodulatory molecule.},
  author       = {Frendéus, Katarina H and Wallin, Hanna and Janciauskiene, Sabina and Abrahamson, Magnus},
  issn         = {1878-5875},
  language     = {eng},
  pages        = {2262--2269},
  publisher    = {ARRAY(0x8ca54c8)},
  series       = {International Journal of Biochemistry and Cell Biology},
  title        = {Macrophage Responses to Interferon-gamma are Dependent on Cystatin C Levels.},
  url          = {http://dx.doi.org/10.1016/j.biocel.2009.05.005},
  volume       = {41},
  year         = {2009},
}