The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. == References == == Associated Data == This section collects any data citations, data availability statements, or supplementary materials included in this article. == Supplementary Materials == Kaplan-Meier survival curves for bleomycin-exposed WT (n = 27) orH-PGDS-/-(n = 19) mice. alteration in interstitial spaces ultimately leads to impairment of gas exchange and death. It is believed that transforming growth factor- (TGF-) plays a dominant role in the pathogenesis of pulmonary fibrosis by promoting proliferation and activation of fibroblasts and inducing epithelial-to-mesenchymal transition of epithelial cells. There has been little progress in treatment approach to directly modulate TGF- signaling [1], and the fatality rate is still high. Therefore , understanding of more detailed mechanism of pulmonary fibrosis development is needed to provide therapeutic options other than organ transplantation to patients with this disease. Inflammation is an important biological response against infection and tissue damage. Suppression or defect of inflammation fails to protect against infection and to heal wounds. On the other hand, chronic and/or excessive inflammation may lead to a variety of diseases from upper airway inflammation to cancer. Whereas idiopathic pulmonary fibrosis progresses without manifesting detectable inflammatory responses, CPI-613 many other forms of pulmonary fibrosis are associated with expression of inflammatory mediators such as tumor necrosis factor-alpha (TNF-) [2], interleukin-1beta (IL-1) [3], and interleukin-17 [4], and infiltration of inflammatory cells such as neutrophils, macrophages, and T cells [5]. Thus, inflammation is assumed to be crucial in progression of at least some types of pulmonary fibrosis [6]. Prostaglandins (PGs) are cyclooxygenase (COX)-dependent arachidonic acid metabolites that play crucial roles in inflammatory responses. PGs, particularly those mediated by COX-2 induction, are implicated in the pathogenesis of pulmonary fibrosis. PGE2[711] and prostacyclin [1214] have been shown to inhibit activation and proliferation of lung fibroblastsin vitroandin festn. In contrast, PGF2is identified as an important mediator of pulmonary fibrosis by enhancing proliferation and collagen synthesis of lung fibroblasts through F-prostanoid receptor in a TGF–independent manner [15]. PGD2is another COX metabolite which is synthesized by its specific enzymes. Hematopoietic PGD CPI-613 synthase Rabbit polyclonal to RIPK3 (H-PGDS) is a cytosolic protein and responsible for PGD2production in hematopoietic linage cells including mast cells [16] and Th2 lymphocytes [17]. PGD2stimulates chemotaxis of eosinophils, basophils, and Th2 lymphocytes, resulting in enhanced inflammation [18]. PGD2is also known as an inflammatory mediator of allergic asthma [19]. In contrast to these pro-inflammatory effects, PGD2is reported to inhibit the activation of inflammatory cells such as antigen-specific T cells [20] and basophils [21]. PGD2also inhibits tumor angiogenesis by suppressing vascular leakage and production of TNF- [22]. The multifaceted actions of PGD2in inflammatory processes are influenced by many factors such that expression level of its synthase, type of inflammatory stimuli, and the phase of the disease [23]. We have previously demonstrated that PGD2inhibits inflammatory responses in endotoxin-induced acute lung injury including vascular hyper-permeability, immune cell infiltration, and cytokine production. Enhancement of anti-inflammatory PGD2signal has proved to be beneficial in treating acute lung injury [24]. Inflammatory response including epithelial cell injury and subsequent infiltration of neutrophils and macrophages also plays an important part in triggering pulmonary fibrosis [25, 26]. These observations prompt us to investigate the roles of PGD2in pulmonary fibrosis. Here, by using bleomycin-induced lung inflammation CPI-613 and pulmonary fibrosis model in mice, we revealed that PGD2plays a protective role by suppressing inflammation. == Materials and Methods == == Ethics Statement == All pet experiments were approved by the Institutional Pet Care and Use Committees of The University of Tokyo (approval no . p11-578) and performed according to the National Institute of Health guidelines. Mice were kept with irradiated food and bedding in the animal room with a light cycle of 12L/12D. Veterinary care.