HtpG, the Porphyromonas gingivalis HSP-90 homologue, induces the chemokine CXCL8 in human monocytic and microvascular vein endothelial cells.
CXCL8 (interlukin 8, IL-8) has a diverse spectrum of biological activities including T cell, neutrophil and basophil chemotactic properties. It is produced by a wide variety of cell types and plays a significant role in the initiation of the acute inflammatory response. During inflammation, CXCL8 attracts and activates leukocytes at the site of infection leading to leukocyte infiltration, which can lead to tissue damage. Porphyromonas gingivalis, an aetiological agent of periodontitis, induces production of CXCL8 from several types of cells via its LPS and outer membrane proteins. Bacterial chaperones elicit a strong pro-inflammatory response in cells of the innate immune system. In P. gingivalis the htpG gene codes for the homologue of human Hsp90, a chaperone that associates with transcription factors, hormone receptors and protein kinases, affecting signal transduction pathways. CXCL8 mRNA and CXCL8 protein production was induced in monocytic/human microvascular vein endothelial cells treated with P. gingivalis cells or rHtpG protein. Blocking of receptors CD91 and TLR4 reduced the production of CXCL8 by rHtpG either using receptor-specific antibody or by siRNA silencing. Pre-incubation of P. gingivalis rHtpG preparations with human anti-HtpG significantly inhibited CXCL8 production. A P. gingivalis HtpG disruption mutant also induced less CXCL8 mRNA and protein. These results suggest that P. gingivalis HtpG might be involved in CXCL8-mediated immunopathogenesis.
Shelburne
Charles E
CE
Department of Biologic and Materials Sciences, School of Dentistry, The University of Michigan, Ann Arbor, MI 48108, USA. ceshelbu@umich.edu
Coopamah
Malini D
MD
Sweier
Domenica G
DG
An
Florence Y-P
FY
Lopatin
Dennis E
DE
D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology*; D016866:Bacteroidaceae Infections / Q000097:blood / Q000276:immunology*; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000276:immunology*; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D014680:Veins / Q000166:cytology
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; C508606:CXCL8 protein, human; D018841:HSP90 Heat-Shock Proteins; D007074:Immunoglobulin G; D016209:Interleukin-8; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; C066720:HtpG protein, bacteria