Regulation of chemokine gene expression and secretion in Staphylococcus aureus-infected osteoblasts.
Staphylococcus aureus is the major cause of osteomyelitis or bone infection, leading to major morbidity, often in children. Little is known about immunopathogenesis of osteomyelitis, although uncontrolled inflammation is a major clinical feature. This study investigated effects of dexamethasone, PGE(2) and T(h)2 cytokines, all potential down-regulatory mediators, on control of S. aureus-induced C-X-C (CXCL8, CXCL10) and C-C (CCL5, CCL2) chemokine gene expression and secretion from human osteoblastic MG-63 cells and primary NHOst cells. Chemokine mRNA expression and secretion were reduced 50-75% by dexamethasone, whereas PGE(2) doubled mRNA accumulation, as detected by RNase protection assay and RT-PCR, but decreased chemokine secretion 33-71% (P < 0.05). IL-10 reduced chemokine mRNA accumulation by 20-40% in MG-63 cells. IL-4 and -13 decreased CXCL8 but not CXCL10 gene expression. IL-10 and IL-13 reduced S. aureus-induced osteoblast C-X-C chemokine secretion, whereas IL-4 decreased CXCL8 secretion 2.5-fold and increased CXCL10 secretion 3-fold (all P < 0.05). In contrast, T(h)2 cytokines increased C-C chemokine secretion from MG-63 osteoblastic cells (P < 0.05), and IL-4 and IL-13 caused similar up-regulation of CCL2 secretion from primary osteoblasts. In summary, during S. aureus infection of osteoblasts, T(h)2 cytokines, dexamethasone and PGE(2) have diverse, sometime upregulatory actions on C-C and C-X-C chemokines due to both pre- and post-transcriptional effects on chemokine secretion.
Wright
Kathleen M
KM
Department of Infectious Diseases, Faculty of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Friedland
Jon S
JS
D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D018418:Th2 Cells / Q000276:immunology
C111835:CCL2 protein, human; C483024:CCL5 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D003907:Dexamethasone; D015232:Dinoprostone