Clinical Relevance of Plasma Prostaglandin F2α Metabolite Concentrations in Patients with Idiopathic Pulmonary Fibrosis

Abstract

BackgroundIdiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology with few current treatment options. Recently, we determined an important role of prostaglandin F2α (PGF2α) in pulmonary fibrosis by using a bleomycin-induced pulmonary fibrosis model and found an abundance of PGF2α in bronchoalveolar lavage fluid of IPF patients. We investigated the role of PGF2α in human IPF by assessing plasma concentrations of 15-keto-dihydro PGF2α, a stable metabolite of PGF2α.MethodsWe measured plasma concentrations of 15-keto-dihydro PGF2α in 91 IPF patients and compared these values with those of controls (n = 25). We further investigated the relationships of plasma 15-keto-dihydro PGF2α concentrations with disease severity and mortality.ResultsPlasma concentrations of 15-keto-dihydro PGF2α were significantly higher in IPF patients than controls (p<0.001). Plasma concentrations of this metabolite were significantly correlated with forced expiratory volume in 1 second (Rs [correlation coefficient] = −0.34, p = 0.004), forced vital capacity (Rs = −0.33, p = 0.005), diffusing capacity for carbon monoxide (Rs = −0.36, p = 0.003), the composite physiologic index (Rs = 0.40, p = 0.001), 6-minute walk distance (Rs = −0.24, p = 0.04) and end-exercise oxygen saturation (Rs = −0.25, p = 0.04) when patients with emphysema were excluded. Multivariate analysis using stepwise Cox proportional hazards model showed that a higher composite physiologic index (relative risk = 1.049, p = 0.002) and plasma 15-keto-dihydro PGF2α concentrations (relative risk = 1.005, p = 0.002) were independently associated with an increased risk of mortality.ConclusionsWe demonstrated significant associations of plasma concentrations of PGF2α metabolites with disease severity and prognosis, which support a potential pathogenic role for PGF2α in human IPF.

Prostaglandin F2α Agonists Negatively Modulate the Size of 3D Organoids from Primary Human Orbital Fibroblasts

“…In fact, it was previously reported that PGF2α facilitates pulmonary fibrosis through the FP receptor in a murine bleomycin-induced pulmonary fibrosis model in which the promoter activity of COL-1 was enhanced. [50][51][52] In conclusion, our newly developed 3D cell culture of HOFs provided us with a better understanding of the molecular etiology of DUES by PG analogs, and its treatment and prevention using this methodology will be our subsequent project.…”

Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways

“…The clinical relevance of PGF2α in PF was investigated by measuring levels of 15-keto-dihydro PGF2α, a major and stable metabolite of PGF2α in plasma of IPF patients. Plasma concentrations of 15-keto-dihydro PGF2α were significantly higher in IPF patients than controls, which correlated with forced expiratory volume in 1 s, forced vital capacity, diffusing capacity for carbon, the composite physiologic index, 6 min walk distance, and end-exercise oxygen saturation [84]. Thus, an association of plasma PGF2α metabolite, 15-keto-dihydro-PGF2α with disease severity of IPF and prognosis, supports a potential pathogenic role for PGF2α in human IPF.…”

Investigation of vitamin B6 inadequacy, induced by exposure to the anti-B6 factor 1-amino d-proline, on plasma lipophilic metabolites of rats: a metabolomics approach

“…The concentration and profile of prostaglandins change drastically during an inflammatory response. In general, they are elevated immediately in an acute inflammation before the recruitment of leukocytes and are therefore considered to be important biomarkers for inflammation and oxidative stress conditions [36]. Interestingly, vitamin B 6 deficiency has been shown to modulate the biosynthesis of prostaglandins in the body, with the direction of changes dependent on the specific prostaglandin under study [37,38].…”