Proinflammatory Cytokine Gene Expression by Murine Macrophages in Response to Brugia malayi Wolbachia Surface Protein

Wolbachia, an endosymbiotic bacterium found in most species of filarial parasites, is thought to play a significant role in inducing innate inflammatory responses in lymphatic filariasis patients. However, the Wolbachia-deriv...

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Main Authors: Chantima Porksakorn, Surang Nuchprayoon, Kiwon Park, Alan L. Scott
Format: Article
Language:English
Published: Wiley 2007-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2007/84318
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author Chantima Porksakorn
Surang Nuchprayoon
Kiwon Park
Alan L. Scott
author_facet Chantima Porksakorn
Surang Nuchprayoon
Kiwon Park
Alan L. Scott
author_sort Chantima Porksakorn
collection DOAJ
description Wolbachia, an endosymbiotic bacterium found in most species of filarial parasites, is thought to play a significant role in inducing innate inflammatory responses in lymphatic filariasis patients. However, the Wolbachia-derived molecules that are recognized by the innate immune system have not yet been identified. In this study, we exposed the murine macrophage cell line RAW 264.7 to a recombinant form of the major Wolbachia surface protein (rWSP) to determine if WSP is capable of innately inducing cytokine transcription. Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) mRNAs were all upregulated by the rWSP stimulation in a dose-dependant manner. TNF transcription peaked at 3 hours, whereas IL-1β and IL-6 transcription peaked at 6 hours post-rWSP exposure. The levels of innate cytokine expression induced by a high-dose (9.0 μg/mL) rWSP in the RAW 264.7 cells were comparable to the levels induced by 0.1 μg/mL E. coli-derived lipopolysaccharides. Pretreatment of the rWSP with proteinase-K drastically reduced IL-1β, IL-6, and TNF transcription. However, the proinflammatory response was not inhibited by polymyxin B treatment. These results strongly suggest that the major Wolbachia surface protein molecule WSP is an important inducer of innate immune responses during filarial infections.
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language English
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spelling doaj-art-3a64814b7a85432d81fd5313d191ddb42025-02-03T05:47:10ZengWileyMediators of Inflammation0962-93511466-18612007-01-01200710.1155/2007/8431884318Proinflammatory Cytokine Gene Expression by Murine Macrophages in Response to Brugia malayi Wolbachia Surface ProteinChantima Porksakorn0Surang Nuchprayoon1Kiwon Park2Alan L. Scott3Lymphatic Filariasis Research Unit, Department of Parasitology, and Chulalongkorn Medical Research Center, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandLymphatic Filariasis Research Unit, Department of Parasitology, and Chulalongkorn Medical Research Center, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USAWolbachia, an endosymbiotic bacterium found in most species of filarial parasites, is thought to play a significant role in inducing innate inflammatory responses in lymphatic filariasis patients. However, the Wolbachia-derived molecules that are recognized by the innate immune system have not yet been identified. In this study, we exposed the murine macrophage cell line RAW 264.7 to a recombinant form of the major Wolbachia surface protein (rWSP) to determine if WSP is capable of innately inducing cytokine transcription. Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) mRNAs were all upregulated by the rWSP stimulation in a dose-dependant manner. TNF transcription peaked at 3 hours, whereas IL-1β and IL-6 transcription peaked at 6 hours post-rWSP exposure. The levels of innate cytokine expression induced by a high-dose (9.0 μg/mL) rWSP in the RAW 264.7 cells were comparable to the levels induced by 0.1 μg/mL E. coli-derived lipopolysaccharides. Pretreatment of the rWSP with proteinase-K drastically reduced IL-1β, IL-6, and TNF transcription. However, the proinflammatory response was not inhibited by polymyxin B treatment. These results strongly suggest that the major Wolbachia surface protein molecule WSP is an important inducer of innate immune responses during filarial infections.http://dx.doi.org/10.1155/2007/84318
spellingShingle Chantima Porksakorn
Surang Nuchprayoon
Kiwon Park
Alan L. Scott
Proinflammatory Cytokine Gene Expression by Murine Macrophages in Response to Brugia malayi Wolbachia Surface Protein
Mediators of Inflammation
title Proinflammatory Cytokine Gene Expression by Murine Macrophages in Response to Brugia malayi Wolbachia Surface Protein
title_full Proinflammatory Cytokine Gene Expression by Murine Macrophages in Response to Brugia malayi Wolbachia Surface Protein
title_fullStr Proinflammatory Cytokine Gene Expression by Murine Macrophages in Response to Brugia malayi Wolbachia Surface Protein
title_full_unstemmed Proinflammatory Cytokine Gene Expression by Murine Macrophages in Response to Brugia malayi Wolbachia Surface Protein
title_short Proinflammatory Cytokine Gene Expression by Murine Macrophages in Response to Brugia malayi Wolbachia Surface Protein
title_sort proinflammatory cytokine gene expression by murine macrophages in response to brugia malayi wolbachia surface protein
url http://dx.doi.org/10.1155/2007/84318
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AT kiwonpark proinflammatorycytokinegeneexpressionbymurinemacrophagesinresponsetobrugiamalayiwolbachiasurfaceprotein
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