Abstract
A similar immune response is implicated in the pathogenesis of pulmonary fibrosis and allergic disorders. We investigated the potential therapeutic efficacy and mechanism of rupatadine, a dual antagonist of histamine and platelet-activation factor (PAF), in bleomycin- (BLM-) and silica-induced pulmonary fibrosis. The indicated dosages of rupatadine were administered in rodents with bleomycin or silica-induced pulmonary fibrosis. The tissue injury, fibrosis, inflammatory cells and cytokines, and lung function were examined to evaluate the therapeutic efficacy of rupatadine. The anti-fibrosis effect of rupatadine was compared with an H1 or PAF receptor antagonist, and efforts were made to reveal rupatadine’s anti-fibrotic mechanism. Rupatadine promoted the resolution of pulmonary inflammation and fibrosis in a dose-dependent manner, as indicated by the reductions in inflammation score, collagen deposition and epithelial-mesenchymal transformation, and infiltration or expression of inflammatory cells or cytokines in the fibrotic lung tissue. Thus, rupatadine treatment improved the declined lung function and significantly decreased animal death. Moreover, rupatadine was able not only to attenuate silica-induced silicosis but also to produce a superior therapeutic efficacy compared to pirfenidone, histamine H1 antagonist loratadine, or PAF antagonist CV-3988. The anti-fibrotic action of rupatadine might relate to its attenuation of BLM- or PAF-induced premature senescence because rupatadine treatment protected against the in vivo and in vitro activation of the p53/p21-dependent senescence pathway. Our studies indicate that rupatadine promotes the resolution of pulmonary inflammation and fibrosis by attenuating the PAF-mediated senescence response. Rupatadine holds promise as a novel drug to treat the devastating disease of pulmonary fibrosis.
Highlights
Pulmonary fibrosis is a chronic interstitial lung disease, which can be induced by a diversity of insults, including microbial infection, smoke, chemical materials, and environment contamination, and is a major structure basis for many chronic fibroproliferative lung diseases [1,2]
Pulmonary fibrosis is driven by chronic inflammation by the heterogenic properties of pathogens, immune cells, and soluble factors [1]
Many soluble factors released from these immune cells participate in the development of allergic diseases and pulmonary fibrosis [12,13,14,15]
Summary
Pulmonary fibrosis is a chronic interstitial lung disease, which can be induced by a diversity of insults, including microbial infection, smoke, chemical materials, and environment contamination, and is a major structure basis for many chronic fibroproliferative lung diseases [1,2]. The mechanism responsible for the pathogenesis of pulmonary fibrosis remains unclear. Immunosuppressive agents have been recommended as a therapeutic regimen, the anti-fibrotic efficacy of this strategy is limited [3]. There is an urgent need for developing new anti-fibrotic therapeutics for these fibroproliferative lung diseases. Many studies demonstrate that tissue fibrosis is mainly driven by chronic inflammation and that the type of immune response is a critical factor affecting the pathogenesis of pulmonary fibrosis [4]. The Th17type immune response participates in the pathogenesis of pulmonary fibrosis by a mechanism that is similar to the Th2type response [7]. The manipulation of immune responses may be a promising therapeutic strategy for the prevention and treatment of pulmonary fibrosis [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
