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Regulation of monocyte chemokine and MMP‐9 secretion by proinflammatory cytokines in tuberculous osteomyelitis
Author(s) -
Wright Kathleen M.,
Friedland Jon S.
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0903433
Subject(s) - proinflammatory cytokine , ccl2 , monocyte , chemokine , interleukin 8 , biology , secretion , tumor necrosis factor alpha , immunology , cxcl10 , cxcl14 , cytokine , microbiology and biotechnology , inflammation , endocrinology
Tuberculous osteomyelitis causes bony destruction as a result of interactions among the pathogen, resident bone cells, and influxing leukocytes. Recruitment of monocytes and T cells is critical for antimycobacterial granuloma formation, but little is known about mechanisms regulating this in bone. We investigated the role of tumor necrosis factor α (TNF‐α) and interleukin (IL)‐1, key cytokines in granuloma formation, in networks involving human osteoblasts and monocytes. Experiments focused on CXC ligand (CXCL)8, CCL2, and matrix metalloproteinase (MMP)‐9, human monocyte‐derived mediators involved in control of leukocyte influx. TNF‐α but not IL‐1 has a key role stimulating CXCL8 secretion in Mycobacterium tuberculosis ‐infected human osteoblast MG‐63 cells. Conditioned medium from M. tuberculosis ‐infected osteoblasts (COBTB) drives CXCL8 and some CCL2 gene expression and secretion from primary human monocytes. IL‐1 receptor antagonist and to a lesser extent anti‐TNF‐α inhibited COBTB‐induced CXCL8 secretion ( P <0.01) but did not affect gene expression. IL‐1 blockade had a comparatively lesser effect on CCL2 secretion, whereas anti‐TNF decreased CCL2 concentrations from 7840 ± 140 to 360 ± 80 pg/ml/4 × 10 5 cells. Neither proinflammatory mediator affects MMP‐9 secretion from COBTB‐stimulated human monocytes. In summary, in a paracrine network, M. tuberculosis ‐infected osteoblasts drive high‐level CXCL8, comparatively less CCL2, but do not alter MMP‐9 secretion from uninfected human monocytes. This network is, in part, regulated by IL‐1 and TNF‐α.