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Novel Roles of Osteopontin and CXC Chemokine Ligand 7 in the Defense against Mycobacterial Infection

ABSTRACT: Granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced human monocyte-derived macrophage (GM-Mphage) or macrophage CSF (M-CSF)-induced human monocyte-derived Mphage (M-Mphage) are distinct in terms of the resistance to Mycobacterium tuberculosis (M. tuberculosis). To elucidate the role of molecules involved in the functional differences between these Mphages, we investigated the gene expression profiles using microarray. After culture of CD14+ monocytes with CSFs, Mphages were cultured with or without BCG (GM-Mf-BCG and M-Mf-BCG). The gene expression profiles from these cells were compared. Chemokines highly expressed in M-Mphages were selected and evaluated for antimycobacterial activity and superoxide production. FN1 and FCGR2B were the most up-regulated genes in GM-Mphage and M-Mphage, respectively. After the stimulation with BCG, 3 chemokine genes (Osteopontin (SPP1), CXC chemokine ligand 7 (CXCL7), and CC chemokine ligand 11 (CCL11)) were highly expressed in M-Mphage-BCG when compared to those in GM-Mf-BCG. A significantly increased resistance to M. tuberculosis H37Ra was observed after the stimulation of GM-Mphage with SPP1 or CXCL7. Superoxide production levels of SPP1- or CXCL7-stimulated GM-Mphages were higher than those of GM-Mphages without stimulation. These results indicate that both SPP1 and CXCL7 might have a role in the resistance against mycobacteria, at least in part, through augmenting reactive oxygen intermediates production in Mphages.

ORGANISM(S): Homo sapiens

PROVIDER: GSE3408 | GEO | 2005/10/05

SECONDARY ACCESSION(S): PRJNA93427

REPOSITORIES: GEO

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