Decreased expression of CCL17 in the disrupted nasal polyp epithelium and its regulation by IL-4 and IL-5.

BACKGROUND:In airway epithelium, thymus and activation-regulated chemokine (CCL17) and macrophage-derived chemokine (CCL22) are induced by defective epithelial barriers such as E-cadherin and attract the effector cells of Th2 immunity. However, the association between the epithelial barrier and CCL17 expression has not been studied in chronic rhinosinusitis with nasal polyp (CRSwNP). Thus, we aimed to evaluate the expression of CCL17 and its regulation by Th cytokines in nasal polyp (NP) epithelial cells. METHODS:The expression and distribution of CCL17, CCL22, E-cadherin and/or epidermal growth factor receptor (EGFR) were measured using real-time PCR, western blot, and immunohistochemistry and compared between normal ethmoid sinus epithelium and NP epithelium. In addition, the expression level of CCL17 was determined in cultured epithelial cells treated with IL-4, IL-5, IL-13, TNF-α, and IFN-γ. RESULTS:The expression of CCL17 was decreased in the NP epithelium compared to the epithelium of normal ethmoid sinus, whereas the expression of CCL22 was not decreased. E-cadherin was differentially distributed between the epithelium of normal ethmoid sinus and NP epithelium. EGFR was also decreased in NPs. Interestingly, the stimulation of cultured epithelial cells with Th2 cytokines, IL-4 and IL-5, resulted in an upregulation of CCL17 expression only in NP epithelial cells whereas the expression of CCL17 was increased in both normal epithelial cells and NP epithelial cells by Th1 cytokines. CONCLUSION:Our results suggest that the decreased expression of CCL17 in defective NP epithelium may be closely connected to NP pathogenesis and can be differentially regulated by cytokines in the NP epithelium of patients with CRSwNP

Analysis of CCL17 expression in epithelial cells treated with DECMA or cytokines.

<p>Epithelial cells from the normal ethmoid were incubated with DECMA, anti-E-cadherin antibody, and the cell extract was analysed by immunoblotting with anti-E-cadherin and anti-CCL17 antibody. Representative immunoblot images (A) and graphical and statistical analysis of relative CCL17 expression (B). Epithelial cells from the normal ethmoid (C) and nasal polyp (D) were treated with Th1 cytokines TNF-α and IFN-γ or Th2 cytokines IL-4, IL-5 and IL-13 as indicated. The expression of IL-4 and IL-5 in nasal polyp epithelial cells was significantly greater than that of normal ethmoid epithelial cells. * <i>p</i><0.05.</p

Immunoblotting analysis of E-cadherin, CCL17, and EGFR in epithelial cells from normal ethmoid and nasal polyp cells.

<p>Representative immunoblot images (A) and graphical and statistical analysis of relative CCL17 expression (B), relative mature E-cadherin expression (C), the ratio of cleaved E-cadherin to mature E-cadherin (D), and relative EGFR expression (E). * <i>p</i><0.05.</p

Patients characteristics.

<p>Patients characteristics.</p