title: Differential regulation of chemokine secretion in tuberculous and staphylococcal osteomyelitis.
abstract: 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 x 10(5) cells, 74,130 +/- 8480 pg/ml per 4 x 10(5) cells, 18,330 +/- 3040 pg/ml per 4 x 10(5) cells, and 138,670 +/- 13,340 pg/ml per 4 x 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 x 10(5) cells, 11,570 +/- 1240 pg/ml per 4 x 10(5) cells, 930 +/- 34 pg/ml per 4 x 10(5) cells, and 13,770 +/- 720 pg/ml per 4 x 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.
authors.affiliation: Department of Infectious Diseases, Faculty of Medicine, Imperial College of Science Technology and Medicine, Hammersmith Hospital, London, United Kingdom.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Wright
authors.forename: Jon S
authors.initials: JS
authors.lastname: Friedland
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054357:Chemokine CXCL10; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000276:immunology / Q000378:metabolism; D010019:Osteomyelitis / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014394:Tuberculosis, Osteoarticular / Q000235:genetics / Q000276:immunology*
chemical_list: D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D016209:Interleukin-8; D012333:RNA, Messenger; D018808:Transcription Factor AP-1