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Differential Regulation of Chemokine Secretion in Tuberculous and Staphylococcal Osteomyelitis
Author(s) -
Wright Kathleen M.,
Friedland Jon S.
Publication year - 2002
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2002.17.9.1680
Subject(s) - chemokine , secretion , staphylococcus aureus , microbiology and biotechnology , monocyte , immunology , chemotaxis , inflammation , mycobacterium tuberculosis , interleukin 8 , chemistry , biology , medicine , tuberculosis , endocrinology , receptor , bacteria , pathology , genetics
Bone infection or osteomyelitis is characterized by uncontrolled inflammation and destructive bone loss although little is known about immunopathogenesis of infection. We investigated control of chemokine secretion from osteoblasts infected with either Mycobacterium tuberculosis , which normally elicits a granulomatous host response, or Staphylococcus aureus , which drives a host response dominated by neutrophil influx. We show that M. tuberculosis infection of cultured and primary osteoblasts induces extensive secretion of the chemokines interleukin (IL)‐8, inducible protein (IP) 10, RANTES, and monocyte chemoattractant protein (MCP) 1 within 72 h (1630 ± 280 pg/ml per 4 × 10 5 cells, 74,130 ± 8480 pg/ml per 4 × 10 5 cells, 18,330 ± 3040 pg/ml per 4 × 10 5 cells, and 13,8670 ± 13,340 pg/ml per 4 × 10 5 cells, respectively, for MG‐63 osteoblasts). S. aureus infection also results in secretion of these chemokines but secretion is delayed and of lesser magnitude (210 ± 10 pg/ml per 4 × 10 5 cells, 11,570 ± 1240 pg/ml per 4 × 10 5 cells, 930 ± 34 pg/ml per 4 × 10 5 cells, and 13,770 ± 720 pg/ml per 4 × 10 5 cells for IL‐8, IP‐10, RANTES, and MCP‐1, respectively). The minimal up‐regulation of secretion of the neutrophil attractant IL‐8 in staphylococcal infection is both striking and unexpected. In both infections, chemokine secretion was dependent on the presence of live organisms. Differences in kinetics and magnitude of chemokine secretion are associated with distinct patterns of mRNA expression, as assessed by ribonuclease protection assay (RPA) and reverse‐transcription polymerase chain reaction (RT‐PCR). In addition, nuclear localization of the transcription factor activator protein (AP) 1 in M. tuberculosis ‐infected osteoblasts also is distinct as compared with S. aureus ‐infected cells. In summary, this study shows that osteoblasts have an important pathogen‐specific role in control of chemokine gene expression and secretion during the human immune response to osteomyelitis.