Pleural tuberculosis (TB) as well as lymphatic TB constitutes more than

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 [1] [2]. The development of PEs is often associated with the accumulation of fluid enriched in proteins and cells in the pleural space [3]. 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 [4] [5]. It is well known that bacterial host and environmental factors influence the development of TB [6]. 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 [8]. Increasing evidence suggests that several Th subsets including Th17 cells [9] regulatory T cells[10] Th9 cells [11] and Th22 cells [12] 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) [13] [14] [15] [16] [17]. 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 [18] [19]. 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 [20] [21] [22]. 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.