Pleural tuberculosis (TB) as well as lymphatic TB constitutes more than half of all extrapulmonary cases. CCR5 the primary receptor used by MCP-2/CCL8 is mostly expressed on pleural CD4+ T lymphocytes. Furthermore we found that infection with either Bacillus Calmette-Guérin (BCG) or H37Rv induced production of MCP-2/CCL8 at both transcriptional and protein level in Mouse monoclonal to CK17 Raw264.7 and THP-1 macrophage cells mouse peritoneal macrophages as well as human PBMC monocyte-derived macrophages (MDMs). The induction of MCP-2/CCL8 by mycobacteria is dependent on the activation of TLR2/PI3K/Akt and p38 signaling pathway. We conclude that accumulation of MCP-2/CCL8 in TB-PEs may function as a biomarker for TB diagnosis. Introduction Tuberculosis (TB) continues to prevail as a major cause of mortality around the world killing almost 1.5 million people annually. Despite implementation of control programs and the availability of effective drugs some 14% of TB patients suffer from tuberculous pleuritis which presents as an acute illness characterized by fever cough pleural chest pain and pleural effusions (PEs). TB-PEs occur in approximately 2-10% of TB patients which may result from primary or reactivation TB  . The development of PEs is often associated with the accumulation of fluid enriched in proteins and cells in the pleural space . It has been well documented that TB and cancer represent the two most frequent causes of exudative PEs predominated by lymphocytes in pleural fluid; whereas PEs during acute infections including empyema and parapneumonic effusions are typically characterized by influx of neutrophils  . It is well known that bacterial host and environmental factors influence the development of TB . TB-PEs are caused by severe delayed-type hypersensitivity (DTH) reactions to the rupture of the subpleural focus of (by means of activation of infected macrophages by Th1-type cytokines. However Th1 cells alone do not explain the resistance/susceptibility to infection and TB disease . Increasing evidence suggests that several Th subsets including Th17 cells  regulatory T cells Th9 cells  and Th22 cells  are involved in the pathogenesis of TB-PEs. A healthy pleural fluid contains few if any T cells. However in TB-PEs T cells preponderate which are sequestrated in this compartment from both systemic and pulmonary vasculature on the visceral pleural surface and from systemic vessels from the parietal pleural surface. AMG-47a Homing of T cells to sites of infection and inflammation is incompletely understood. Chemokines are proinflammatory cytokines of low molecular size which AMG-47a orchestrate migration and activation of different leukocyte populations. On the basis of the number and arrangement of conserved cysteins chemokines can be divided into four groups; CXC CC C and CX3C. Both the CXC and CC families contain many members whereas lymphotactin and fractalkine/neurotactin are at present the only known C and CX3C chemokines respectively. It has been reported that multiple chemokines expressed in the TB-PEs including CXC chemokines such as IFN-γ-inducible protein of 10-kD (IP-10/CXCL10) monokine induced by IFN-γ (MIG/CXCL9) IFN-inducible T-cell alpha chemoattractant (I-TAC/CXCL11) interleukin-8 (IL-8/CXCL8) as well as CC chemokiines such as macrophage inflammatory protein-1 alpha (MIP-1alpha/CCL3) regulated upon activation normal T lymphocyte expressed and secreted (RANTES/CCL5) and monocyte chemotactic AMG-47a protein 1 (MCP-1/CCL2)     . Here we performed a protein array analysis of cytokine abundance in the PEs from TB patients and non-TB patients and firstly identified MCP-2/CCL8 as a significantly higher expressed chemokine in the TB-PEs. MCP-2/CCL8 is a proinflammatory chemokine which is expressed in inflamed tissues by resident and infiltrated cells (primarily monocyte/macrophages) after paracrine stimulation from AMG-47a T-cells by IFNs and other proinflammatory cytokines or through innate mechanisms upon contact with viral bacterial and fungal agents  . It is chemotactic for and activates different cell types including granulocytes and mononuclear phagocytes through various chemokine receptors including chemokine receptors CCR1 CCR2B and CCR5   . In this study we describe the source and regulation of MCP-2 as well as the expression of CCR5 which is the primary receptor of MCP-2 on cells accumulated in TB-PEs. Our study provides first hints on the role of MCP-2/CCL8 in the pathogenesis of pleural TB. Results Elevated MCP-2/CCL8.