Chronic rhinosinusitis with nasal polyps and without nasal polyps is associated with increased expression of lysophosphatidic acid-related molecules

Abstract

Background: Chronic sinusitis with nasal polyps (CRSwNPs) or CRS without NPs (CRSsNPs) is associated with expression of various cytokines. Lysophosphatidic acid (LPA) generated by autotaxin (ATX), LPA-producing enzyme, initiates signaling cascade involved in the inflammatory responses and participates in diverse biological processes through LPA receptors, including cytokine production. We analyzed the expression and distribution patterns of LPA-related molecules in nasal secretion and sinus mucosa of normal controls and patients with CRSwNPs and CRSsNPs, to evaluate the possible effects of the ATX-LPA receptor axis on the pathogenesis of CRS. Methods: LPA levels in nasal secretion and the expression and distribution patterns of ATX and LPA receptors 1-3 (LPA1-3) in sinus mucosa were investigated using ELISA, real-time polymerase chain reaction, Western blot, and immunohistochemistry. We elucidated the effect of CRS-relevant cytokines on the expression of ATX and LPA receptors, using cultured sinus epithelial cells, and investigated the effect of LPA on the expression of CRS-relevant cytokines, using sinus mucosa explant culture. Results: LPA, ATX, and LPA1-3 levels are increased in CRSwNPs and CRSsNPs. ATX and LPA1-3 were localized to superficial epithelium, submucosal glands in normal and inflammatory mucosa, but in inflammatory mucosa, they were found in inflammatory cells. LPA1-3 were noted in endothelium. Sinus mucosa explant stimulated with LPA increasingly produced IL-4, IL-5, interferon gamma, and TNF-alpha, and in cultured epithelial cells stimulated with CRS-relevant cytokines, ATX, and LPA1-3 were differentially induced. Conclusion: LPA in human sinus mucosa may play important roles in the pathogenesis of CRS, contributing to produce CRS-related cytokines. LPA-related molecules were increased in CRS, which may attribute to CRS-related cytokines.