Macrophage Responses to Interferon-gamma are Dependent on Cystatin C Levels.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1412253
- author
- Frendéus, Katarina H ; Wallin, Hanna LU ; Janciauskiene, Sabina LU and Abrahamson, Magnus LU
- organization
- publishing date
- 2009
- 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
- 2016-04-04 14:16:03
- date last changed
- 2022-03-31 22:15:29
@article{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 = {{Elsevier}}, 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}}, doi = {{10.1016/j.biocel.2009.05.005}}, volume = {{41}}, year = {{2009}}, }