Expression and function of transforming growth factor β in melioidosis.
Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast Asia and northern Australia. An important controller of the immune system is the pleiotropic cytokine transforming growth factor β (TGF-β), of which Smad2 and...
| Huvudupphovsmän: | , , , , , , , , |
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| Materialtyp: | Journal article |
| Språk: | English |
| Publicerad: |
2012
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| _version_ | 1826272454987743232 |
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| author | Weehuizen, T Wieland, C van der Windt, G Duitman, J Boon, L Day, N Peacock, S van der Poll, T Wiersinga, W |
| author_facet | Weehuizen, T Wieland, C van der Windt, G Duitman, J Boon, L Day, N Peacock, S van der Poll, T Wiersinga, W |
| author_sort | Weehuizen, T |
| collection | OXFORD |
| description | Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast Asia and northern Australia. An important controller of the immune system is the pleiotropic cytokine transforming growth factor β (TGF-β), of which Smad2 and Smad3 are the major signal transducers. In this study, we aimed to characterize TGF-β expression and function in experimental melioidosis. TGF-β expression was determined in 33 patients with culture-proven infection with B. pseudomallei and 30 healthy controls. We found that plasma TGF-β concentrations were strongly elevated during melioidosis. In line with this finding, TGF-β expression in C57BL/6 mice intranasally inoculated with B. pseudomallei was enhanced as well. To assess the role of TGF-β, we inhibited TGF-β using a selective murine TGF-β antibody. Treatment of mice with anti-TGF-β antibody resulted in decreased lung Smad2 phosphorylation. TGF-β blockade appeared to be protective: mice treated with anti-TGF-β antibody and subsequently infected with B. pseudomallei showed diminished bacterial loads. Moreover, less distant organ injury was observed in anti-TGF-β treated mice as shown by reduced blood urea nitrogen (BUN) and aspartate transaminase (AST) values. However, anti-TGF-β treatment did not have an effect on survival. In conclusion, TGF-β is upregulated during B. pseudomallei infection and plays a limited but proinflammatory role during experimental melioidosis. |
| first_indexed | 2024-03-06T22:12:50Z |
| format | Journal article |
| id | oxford-uuid:5265ddc6-ff6c-4db2-bb01-b43f5b8952a1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:12:50Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:5265ddc6-ff6c-4db2-bb01-b43f5b8952a12022-03-26T16:25:24ZExpression and function of transforming growth factor β in melioidosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5265ddc6-ff6c-4db2-bb01-b43f5b8952a1EnglishSymplectic Elements at Oxford2012Weehuizen, TWieland, Cvan der Windt, GDuitman, JBoon, LDay, NPeacock, Svan der Poll, TWiersinga, WMelioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast Asia and northern Australia. An important controller of the immune system is the pleiotropic cytokine transforming growth factor β (TGF-β), of which Smad2 and Smad3 are the major signal transducers. In this study, we aimed to characterize TGF-β expression and function in experimental melioidosis. TGF-β expression was determined in 33 patients with culture-proven infection with B. pseudomallei and 30 healthy controls. We found that plasma TGF-β concentrations were strongly elevated during melioidosis. In line with this finding, TGF-β expression in C57BL/6 mice intranasally inoculated with B. pseudomallei was enhanced as well. To assess the role of TGF-β, we inhibited TGF-β using a selective murine TGF-β antibody. Treatment of mice with anti-TGF-β antibody resulted in decreased lung Smad2 phosphorylation. TGF-β blockade appeared to be protective: mice treated with anti-TGF-β antibody and subsequently infected with B. pseudomallei showed diminished bacterial loads. Moreover, less distant organ injury was observed in anti-TGF-β treated mice as shown by reduced blood urea nitrogen (BUN) and aspartate transaminase (AST) values. However, anti-TGF-β treatment did not have an effect on survival. In conclusion, TGF-β is upregulated during B. pseudomallei infection and plays a limited but proinflammatory role during experimental melioidosis. |
| spellingShingle | Weehuizen, T Wieland, C van der Windt, G Duitman, J Boon, L Day, N Peacock, S van der Poll, T Wiersinga, W Expression and function of transforming growth factor β in melioidosis. |
| title | Expression and function of transforming growth factor β in melioidosis. |
| title_full | Expression and function of transforming growth factor β in melioidosis. |
| title_fullStr | Expression and function of transforming growth factor β in melioidosis. |
| title_full_unstemmed | Expression and function of transforming growth factor β in melioidosis. |
| title_short | Expression and function of transforming growth factor β in melioidosis. |
| title_sort | expression and function of transforming growth factor β in melioidosis |
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