The following is a summary of “Sphingosine-1-phosphate induces airway smooth muscle hyperresponsiveness and proliferation,” published in the November 2023 issue of Allergy & Immunology by Maguire, et al.
Exploration of sphingosine-1-phosphate (S1P) as a potential therapeutic target in asthma and lung diseases has gained momentum due to its role in regulating smooth muscle functions. While animal studies have hinted at the involvement of S1P-mediated signaling in airway smooth muscle (ASM) regulation, airway hyperresponsiveness, and remodeling, evidence from human studies remains scarce. For a study, researchers sought to bridge the gap by comparing airway responsiveness to S1P in healthy and asthmatic individuals in various settings. The assessment was conducted in vivo, ex vivo using isolated human airways and murine airways extracted from healthy and house dust mites (HDM)-sensitized animals.
Measurement of airway responsiveness involved spirometry during inhalation challenges and wire myography in isolated human and mouse airways. Thymidine incorporation and calcium mobilization assays were employed to scrutinize human ASM cell responses.
Contrary to expectations, S1P failed to induce airway constriction in healthy and HDM-exposed human airways. However, a 30-minute exposure to S1P resulted in a concentration-dependent enhancement of airway reactivity to histamine in human airways. Moreover, S1P concentration-dependently amplified the proliferation of human ASM cells, with S1P receptor type 2 identified as the mediating factor through selective antagonism and small-interfering RNA knockdown.
The findings proposed a potential role for locally released S1P in regulating ASM hyperresponsiveness and hyperplasia, opening avenues for novel therapeutic targets in asthma.