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.
The level of difficulty during an endoscopic approach for an inferior orbital fracture depends on the fracture pattern and the presence of a ruptured membrane (orbital periosteum and sinus mucosa). The purpose of our study was to examine fracture patterns according to age group and to determine the relationship between the type of fracture and the type of membrane injury.We reviewed the records of 30 patients who, from 2006 to 2010, underwent endoscopic transantral and transnasal approach with a balloon catheter technique to repair orbital floor fracture. The procedure was done through middle or inferior meatal antrostomy and two small antrostomies made in the anterior wall of the maxillary sinus by using an endoscope and specially designed curved dissectors.There were 3 linear, 20 trapdoor-type and 7 blowout fractures. There was a tendency toward a higher incidence of linear fractures at younger ages and of blowout fractures in older patients. All linear fractures had rupture of both membranes, whereas both membranes were intact in 15 of the 20 patients with trapdoor fractures. Among blowout fractures, there was no membrane rupture in five and both membranes were ruptured in two patients. No patient reported diplopia after fracture repair.Rupture of the periosteum, which makes visualization and reduction of orbital tissue difficult for the surgeon during endoscopic repair of the orbital floor fracture, was observed in 3 of 3 linear fractures and 5 of 20 trapdoor fractures. We found that linear fractures were more common in pediatric patients. Care of pediatric orbital floor fracture requires particular caution.
We hypothesized that differences in the microbiome could be a cause of the substantial differences in the symptoms of and treatment options for adult and pediatric patients with chronic rhinosinusitis (CRS). First, we characterized the differences in the nasal microbiomes of pediatric and adult CRS patients. Swabs were obtained from 19 patients with chronic rhinosinusitis (9 children and 10 adults). The bacterial 16S rRNA gene was pyrosequenced to compare the microbiota of the middle meatus. No significant differences were found in species richness and alpha-diversity indices between the two groups. However, in the comparison of diversity between groups using the unweighted pair group method with arithmetic mean (UPGMA) clustering of microbiome taxonomic profiles, we observed a relatively clear separation between the adult and pediatric groups. Actinobacteria had a significantly higher relative abundance in the adult group than in the pediatric group at the phylum level. At the genus level, Corynebacterium showed significantly higher relative abundance in the adult group than in the pediatric group. This is a comparative study between the microbiomes of adult and pediatric CRS patients. We expect this study to be the first step in understanding the pathogenesis of CRS in adults and children using microbiome analysis.
Background and Objectives We evaluated the symptom improvement, surgical outcomes and post-operative complications of the figure of 8 anchoring suture technique using polycaprolactone (PCL) nasal mesh for the treatment of caudal septal subluxation.Subjects and Method We conducted a retrospective study of patients who underwent between March 2020 and March 2021 endonasal septoplasty using the figure of 8 anchoring suture technique and a PCL nasal mesh as a protective supporting graft. Fourteen patients were divided into two groups, the allergic and non-allergic rhinitis group. Symptom improvements were assessed using the Nasal Obstruction Symptoms Evaluation (NOSE) scores and visual analog scale (VAS) scores for epistaxis and headache. Post-operative patient-reported subjective changes in nasal obstruction were also recorded. All evaluations were conducted one to four months post-operatively.Results Post-operative endoscopic examination revealed that all patients had their septum straightened. The mean post-operative NOSE scores in overall and each item were significantly lower than the mean NOSE scores in the pre-operative period (p<0.05). The mean post-operative NOSE scores for patients both with and without allergic rhinitis were also significantly decreased compared to those in the pre-operative period (p<0.05). A decrease in VAS scores was significant (p=0.008) for headache but not for epistaxis (p=0.141). All patients reported improvement of subjective nasal obstruction post-operatively.Conclusion The use of figure of 8 anchoring suture technique with a PCL nasal mesh as a protective and supportive graft was proven to be a successful method for correcting caudal septal subluxation.
Nasal polyps are associated with chronic inflammation of the sinonasal mucosa and are involved in myofibroblast differentiation and extracellular matrix (ECM) accumulation. Ginsenoside Rg1, a compound derived from Panax ginseng, shows antifibrotic and anticancer effects. However, the molecular effects of Rg1 on myofibroblast differentiation and ECM production remain unknown. The aims of this study were to investigate the effect of Rg1 on transforming growth factor (TGF)- β1-induced myofibroblast differentiation and ECM production and to determine the molecular mechanism of Rg1 in nasal polyp-derived fibroblasts (NPDFs). NPDFs were isolated from nasal polyps of seven patients who had chronic rhinosinusitis with nasal polyp. NPDFs were exposed to TGF- β1 with or without Rg1. Expression levels of α-smooth muscle actin (SMA), fibronectin and collagen type I α1 were determined by reverse transcription polymerase chain reaction, Western blot and immunofluorescent staining. TGF- β1 signaling molecules, including Smad2/3, extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 were analyzed by Western blotting. Transcription factors involved with TGF- β1 signaling, nuclear factor (NF)- κB and activator protein 1 (AP-1) were also assessed by Western blot. The cytotoxic effect of Rg1 was measured by an established viability assay. The mRNA and protein expression levels of α-SMA, fibronectin and collagen type I α1 were increased in TGF- β1-induced NPDFs. Rg1 inhibited these effects. The inhibitory molecular mechanism of Rg1 was involved in the ERK pathway. Rg1 inhibited the transcription factor activation of AP-1. Rg1 itself was not cytotoxic. The ginsenoside Rg1 has inhibitory effects on myofibroblast differentiation and ECM production. The inhibitory mechanism of Rg1 is involved with the ERK and AP-1 signaling pathways. Rg1 may be useful as an inhibitor of ECM deposition, and has potential to be used as a novel treatment option for nasal polyps.
Interleukin (IL)-33 plays an important role in controlling immune responses in barrier tissues, and is a potent mediator of inflammatory diseases such as asthma, rheumatoid disease, and chronic rhinosinusitis. The aims of the present study were 2-fold: (1) to determine the stimulatory effect of tumor necrosis factor-α (TNF-α) on IL-33 production in nasal epithelial and A549 cells; and (2) to identify downstream pathways that activate IL-33 production.Primary nasal epithelial cells (PNECs) from 5 normal patients were isolated and cultured. To identify which cytokines stimulate IL-33 production, we performed reverse-transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. Three mitogen-activated protein kinases (MAPKs) (p38, extracellular signal-regulated kinase [ERK], and c-Jun N-terminal kinase [JNK]) and nuclear factor κB (NF-κB) were evaluated as downstream signaling molecules by RT-PCR, ELISA, Western blot analysis, and luciferase reporter assay.The IL-33 messenger RNA (mRNA) and protein levels were increased significantly by TNF-α in PNECs and A549 cells. TNF-α stimulated the expression of IL-33 in a dose- and time-dependent manner in A549 cells. PNECs and A549 cells were treated with TNF-α in the presence of specific inhibitors of p38, ERK, JNK, and NF-κB. In both cell types, inhibitors of ERK, p38, and NF-κB reversed TNF-α-induced IL-33 production. In the luciferase reporter assay, NF-κB activity was inhibited not only by an NF-κB inhibitor, but also by ERK and p38 inhibitors.TNF-α stimulated IL-33 expression through ERK, p38, and NFκB pathways in PNECs and A549 cells.
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