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Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by fibroblast proliferation and excess deposition of collagen and other extracellular matrix (ECM) proteins, which lead to distorted lung architecture and function (1). Given that anti-inflammatory or immunosuppressive therapy currently used for IPF does not improve disease progression therapies targeted to blocking the mechanisms of fibrogenesis are needed (1). Although transforming growth factor-β. (TGF-β) functions are crucial in fibrosis (2,3), antagonizing this pathway in bleomycin-induced pulmonary fibrosis, an animal model of IPF, does not prevent fibrosis completely (4-7), indicating an additional pathway also has a key role in fibrogenesis. Given that the loss of cytosolic phospholipase [A.sub.2] [(cPLA.sub.2)] suppresses bleomycin-induced pulmonary fibrosis (8), we examined the roles of prostaglandins using mice lacking each prostoaglandin receptor (9-15). Here we show that loss of prostaglandin F (PGF) receptor (FP) selectively attenuates pulmonary fibrosis while maintaining similar levels of alveolar inflammation and TGF-β. stimulation as compared to wild-type (WT) mice, and that FP deficiency and inhibition of TGF-β. signaling additively decrease fibrosis. Furthermore, [PGF.sub.2α] is abundant in bronchoalveolar lavage fluid (BALF) of subjects with IPF and stimulates proliferation and collagen production of lung fibroblasts via FP, independently of TGF-β These findings show that [PGF.sub.2α]-FP signaling facilitates pulmonary fibrosis independently of TGF-β and suggests this signaling pathway as a therapeutic target for IPF., [cPLA.sub.2] cleaves phospholipids in response to stimuli and releases arachidonic acid, which is metabolized by cyclooxygenase (COX) to produce prostaglandins and by 5-lipoxygenase to produce leukotrienes. Prostaglandins, including [PGD.sub.2], [PGE.sub.2], [...]

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by fibroblast proliferation and excess deposition of collagen and other extracellular matrix (ECM) proteins, which lead to distorted lung architecture and function. Given that anti-inflammatory or immunosuppressive therapy currently used for IPF does not improve disease progression therapies targeted to blocking the mechanisms of fibrogenesis are needed. Although transforming growth factor-β (TGF-β) functions are crucial in fibrosis, antagonizing this pathway in bleomycin-induced pulmonary fibrosis, an animal model of IPF, does not prevent fibrosis completely, indicating an additional pathway also has a key role in fibrogenesis. Given that the loss of cytosolic phospholipase A2 (cPLA2) suppresses bleomycin-induced pulmonary fibrosis, we examined the roles of prostaglandins using mice lacking each prostoaglandin receptor. Here we show that loss of prostaglandin F (PGF) receptor (FP) selectively attenuates pulmonary fibrosis while maintaining similar levels of alveolar inflammation and TGF-β stimulation as compared to wild-type (WT) mice, and that FP deficiency and inhibition of TGF-β signaling additively decrease fibrosis. Furthermore, PGF2α is abundant in bronchoalveolar lavage fluid (BALF) of subjects with IPF and stimulates proliferation and collagen production of lung fibroblasts via FP, independently of TGF-β. These findings show that PGF2α-FP signaling facilitates pulmonary fibrosis independently of TGF-β and suggests this signaling pathway as a therapeutic target for IPF. [ABSTRACT FROM AUTHOR]