Furthermore, TAS-115 inhibited the phosphorylation of c-FMS, a receptor of macrophage colony-stimulating factor, in murine bone marrow-derived macrophages and decreased the production of CCL2, another key molecule for inducing pulmonary fibrosis, under the stimulation of macrophage colony-stimulating factor.
Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade of CCL2failed to improve the clinical course of patients with lung fibrosis.
The significantly increased binding of p65 and c-Jun to the CCL2 promoter was also observed in the lung tissue of bleomycin-induced pulmonary fibrosis murine model.
Targeting PAR(1) on the pulmonary epithelium may offer a unique opportunity for therapeutic intervention in pulmonary fibrosis and other inflammatory and fibroproliferative conditions associated with excessive local generation of thrombin and CCL2 release.
A significant negative correlation was observed between the percentage of Dlco and MCP-1 and MIP-1 alpha levels in BAL fluid in patients with PF (r=-0.65, p=0.003; r=-0.48, p=0.04; respectively).
M-CSF-/- and CCL2-/- mice had less lung fibrosis, mononuclear phagocyte recruitment, collagen deposition, and connective tissue growth factor (CTGF) expression after bleomycin administration than wild-type littermates.
In this study, MCP-1 expression in lungs of rats with bleomycin (BLM)-induced pulmonary fibrosis is examined to evaluate its cellular origin and potential role in pathogenesis.