Rat Fractalkine/CX3CL1(Chemokine C-X3-C-Motif Ligand 1) ELISA Kit

Peritoneal dialysis (PD) is limited by chronic fibrotic remodeling of the peritoneal wall, a transforming growth factor-beta (TGF-beta)-mediated process. The fractalkine (CX3CL1) receptor CX3CR1 is expressed on macrophages and monocytes, where it is a marker of TGF beta expression. Detection of its ligand CX3CL1 on the peritoneal mesothelium led us to hypothesize a pathophysiologic role of CX3CL1-CX3CR1 interaction in peritoneal fibrosis. We found that CX3CL1 was expressed on peritoneal mesothelial cells from PD patients and in a murine PD model. CX3CR1, mostly expressed on macrophages in the peritoneal wall, promoted fibrosis induced by chronic dialysate exposure in the mouse model. Our data suggest a positive feedback loop whereby direct interaction with CX3CR1-expressing macrophages promotes mesothelial expression of CX3CL1 and TGF beta expression. In turn, TGF beta upregulates CX3CR1 in murine and human monocytic cells. Upstream, macrophage cytokines including interleukin-1 beta (IL-1 beta) promote mesothelial CX3CR1 and TGF beta expression, providing a starting point for CX3CL1-CX3CR1 interaction. IL-1 beta expression was enhanced by exposure to dialysate both in vitro and in the mouse models. Our data suggest that macrophage-mesothelial cell crosstalk through CX3CR1-CX3CL1 interaction enhances mesothelial TGF beta production, promoting peritoneal fibrosis in response to dialysate exposure. This interaction could be a novel therapeutic target in PD-associated chronic peritoneal fibrosis.

Idiopathic pulmonary fibrosis is a chronic and progressive disease of unknown cause. It is characterized by the aberrant activation of the bronchioalveolar epithelium, the formation of fibroblast foci and the excessive production extracellular matrix. The cellular and molecular mechanisms that contribute to the pathobiology of the disease are unclear. The CX3CL1-CX3CR1 axis regulates cellular responses that are known to be relevant in IPF, such as proliferation and collagen production. In this study, we characterize for the first time the expression of CX3CL1 and its receptor in lung tissue from patients with IPF; and its effect on collagen production in IPF fibroblasts. We found that CX3CL1-CX3CR1 axis has a modified expression in the lung tissue, importantly this axis is expressed on fibroblasts, and CX3CL1 decreased the collagen production in pulmonary fibroblasts derived from IPF patients.