Document Detail


Human herpesvirus 8-derived viral IL-6 induces PTX3 expression in Kaposi's sarcoma cells.
MedLine Citation:
PMID:  12004288     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To analyse if human herpesvirus 8 (HHV8)-derived viral interleukin-6 (vIL-6) has the capacity to activate Kaposi's sarcoma (KS) cells to elicit a local acute-phase response. DESIGN: Proinflammatory activation of KS cells was compared using vIL-6, human IL-6, as well as the complex of human IL-6 with the soluble IL-6 receptor, and expression of the novel acute-phase protein pentraxin-3 (PTX3) was analysed. METHODS: We established primary KS cell cultures from patients with AIDS-associated and classical KS and expressed recombinant HHV8-derived vIL-6 in COS-7 cells. Expression of PTX3 by vIL-6-stimulated KS cell cultures was analysed by quantitative real-time reverse transcriptase-polymerase chain reaction. Mitogenic effects of vIL-6 on the KS cells of distinct aetiology were compared by [3H]thymidine incorporation. RESULTS: We show that vIL-6 induced a marked and sustained expression of the novel acute-phase protein PTX3 in human primary KS cell cultures. vIL-6 directly activated KS cells, which uniquely expressed gp130, the signal-transducing subunit of the IL-6 receptor, but were negative for the IL-6-binding unit (IL-6R). In contrast, human IL-6 did not stimulate KS cells in the absence of the full IL-6R. Expression of PTX3 messenger RNA increased by more than 25-fold in vIL-6-stimulated KS cells after 24 h. Particularly after extended incubation with the virokine, vIL-6 mediated a pronounced mitogenic effect on KS cells. CONCLUSION: The induction of an extrahepatic acute-phase response by vIL-6-activated KS cells may contribute to local tissue damage and the attraction of inflammatory cells, and add to a more aggressive phenotype.
Authors:
Mariam Klouche; Norbert Brockmeyer; Cornelius Knabbe; Stefan Rose-John
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  AIDS (London, England)     Volume:  16     ISSN:  0269-9370     ISO Abbreviation:  AIDS     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-05-10     Completed Date:  2002-06-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  F9-18     Citation Subset:  IM; X    
Affiliation:
Institute of Clinical Pathology, Department of Laboratory Medicine, Robert Bosch Hospital and Robert Bosch Society for Medical Research, Stuttgart, Germany. mariam.klouche@rbk.de
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MeSH Terms
Descriptor/Qualifier:
Acute-Phase Proteins / biosynthesis*
Acute-Phase Reaction
Animals
Antigens, CD / metabolism
C-Reactive Protein / biosynthesis*
COS Cells
Cell Division
Cells, Cultured
Cytokine Receptor gp130
Herpesvirus 8, Human / physiology*
Humans
Interleukin-6 / physiology*
Kinetics
Membrane Glycoproteins / metabolism
Receptors, Interleukin-6 / biosynthesis
Recombinant Proteins
Reverse Transcriptase Polymerase Chain Reaction
Sarcoma, Kaposi / metabolism*
Serum Amyloid P-Component / biosynthesis*
Tumor Cells, Cultured
Viral Proteins / physiology*
Chemical
Reg. No./Substance:
0/Acute-Phase Proteins; 0/Antigens, CD; 0/IL6ST protein, human; 0/Interleukin-6; 0/Membrane Glycoproteins; 0/Receptors, Interleukin-6; 0/Recombinant Proteins; 0/Serum Amyloid P-Component; 0/Viral Proteins; 133483-10-0/Cytokine Receptor gp130; 148591-49-5/PTX3 protein; 9007-41-4/C-Reactive Protein

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