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

Abstract

BackgroundIn 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.MethodsThe 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.ResultsThe 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.ConclusionOur 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.

Mast Cells in Gut and Brain and Their Potential Role as an Emerging Therapeutic Target for Neural Diseases

“…Tryptase can activate PAR-2 on epithelial cells by increasing permeability through TJs (McDermott et al, 2003). Epithelial barrier breakdown is associated with an increase in pro-inflammatory cytokines, including IL-4, Il-13, IFN-γ, and TNF-α (Kim et al, 2018). Further molecules released by MCs, including chymase and prostaglandin D2, modulate epithelial chloride and water secretion and intestinal permeability (Wouters et al, 2016; Dong et al, 2017).…”

Identification of Key Modules, Hub Genes, and Noncoding RNAs in Chronic Rhinosinusitis with Nasal Polyps by Weighted Gene Coexpression Network Analysis

“…In the blue modules, SRC, Smad3, Smad4, AKT1, LRP1, IGF1R, FGFR3, CDH1, NCF1, and ARRB2 were most significantly related to CRSwNP. Except for SRC [5], Smad3 [6], and CDH1 [7], no other genes were found to play a role in the pathogenesis of CRSwNP. In the turquoise module, which included PIK3R1, CDK1, CBL, INSR, VAV1, MDM2, HCK, SOS1, PRKCE, and ITGB2, no genes have been shown to be involved in the development of CRSwNP in the currently published literature studies.…”

“…Because CRSwNP is prone to relapse and brings great pain to patients, it is particularly urgent to understand its molecular mechanism, as well as to promote research on related drugs. Previously, some genes such as SRC [5], SMAD3 [6], and CDH1 [7] have been found to play roles in the pathogenesis of CRSwNP. A study showed that genetic factors might play a role in the higher prevalence of nasal polyps in Asian patients compared with patients from Western countries.…”

Deoxynivalenol and Zearalenone: Different Mycotoxins with Different Toxic Effects in the Sertoli Cells of Equus asinus

“…Our results indicated that DON might have stronger oxidative toxicity than ZEA in Equus asinus SCs. Moreover, several studies have demonstrated that MSH6 (an important component of the mismatch repair system) is a tumour-related factor that can affect tumorigenesis, proliferation, migration, and invasion effects [69]. It is well known that suppression of MSH6 is associated with a variety of tumours [70,71].…”