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1.
Am J Rhinol Allergy ; 36(2): 261-268, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34738483

ABSTRACT

BACKGROUND: Low-level light therapy (LLLT) is widely used for the photobiomodulation of cell behavior. Recent studies have shown that LLLT affects the proliferation and migration of various types of mesenchymal stem cells (MSCs). However, there is a lack of studies investigating the effect of LLT on enhancing the immunomodulatory properties of tonsil-derived MSCs (T-MSCs). OBJECTIVE: The aim of this study was to investigate the immunomodulatory effects of conditioned media from T-MSCs (T-MSCs-CM) treated with LLLT in allergic inflammation. METHODS: We isolated T-MSCs from human palatine tonsils and evaluated the ingredients of T-MSCs-CM. The effect of T-MSCs-CM treated with LLLT was evaluated in a mouse model of allergic rhinitis (AR). We randomly divided the mice into four groups (negative control, positive control, T-MSCs-CM alone, and T-MSCs-CM treated with LLLT). To elucidate the therapeutic effect, we assessed rhinitis symptoms, serum immunoglobulin (Ig), the number of inflammatory cells, and cytokine expression. RESULTS: We identified increased expression of immunomodulatory factors, such as HGF, TGF-ß, and PGE, in T-MSCs-CM treated with LLLT, compared to T-MSCs-CM without LLLT. Our animal study demonstrated reduced allergic symptoms and lower expression of total IgE and OVA-specific IgE in the LLLT-treated T-MSCs-CM group compared to the AR group and T-MSCs-CM alone. Moreover, we found that T-MSCs-CM treated with LLLT showed significantly decreased infiltration of eosinophils, neutrophils, and IL-17 cells in the nasal mucosa and reduced IL-4, IL-17, and IFN-γ expression in OVA-incubated splenocytes compared to the AR group. CONCLUSIONS: The present study suggests that T-MSCs-CM treated with LLLT may provide an improved therapeutic effect against nasal allergic inflammation than T-MSCs-CM alone.


Subject(s)
Anti-Allergic Agents , Mesenchymal Stem Cells , Rhinitis, Allergic , Animals , Anti-Allergic Agents/therapeutic use , Cytokines/metabolism , Disease Models, Animal , Mesenchymal Stem Cells/metabolism , Mice , Mice, Inbred BALB C , Nasal Mucosa/metabolism , Ovalbumin , Palatine Tonsil , Rhinitis, Allergic/drug therapy , Secretome
2.
J Clin Med ; 10(4)2021 Feb 15.
Article in English | MEDLINE | ID: mdl-33671931

ABSTRACT

Allergic rhinitis (AR) is a common disease that interferes with the daily activities and reduces the quality of life. Conventional treatments often do not provide complete resolution of the symptoms, and many new treatment modalities have been tried. This study aimed to evaluate the efficacy and safety of low-level laser therapy (LLLT) for AR in a randomized, double-blind, placebo-controlled trial. Patients diagnosed with AR were randomly allocated to receive LLLT or sham treatment. The primary outcome was a change in the reflective total nasal symptom score (TNSS). The secondary outcome was quality of life scores assessed using the Rhinoconjunctivitis Quality of Life Questionnaire. Incidences of adverse events were also recorded. Among 67 randomized subjects, 41 subjects (22 in LLLT group and 19 in sham treatment group) were included for efficacy analysis. The LLLT group showed a significantly improved TNSS score compared to the sham treatment group for decreasing AR symptom severity (p = 0.011) and improving quality of life regarding nasal symptoms (p = 0.036) at the end of treatment. Throughout the treatment period, no severe adverse events occurred. This clinical trial showed that LLLT is an effective and safe option for the management of AR regarding symptom relief and quality of life improvement.

3.
Thorax ; 75(11): 982-993, 2020 11.
Article in English | MEDLINE | ID: mdl-33023995

ABSTRACT

BACKGROUND: Epithelial to mesenchymal transition (EMT) is associated with the pathophysiology of chronic rhinosinusitis with nasal polyp (CRSwNP). Wnt signaling is causative for EMT, whereas the mechanism in CRSwNP is not fully understood. OBJECTIVE: We sought to evaluate the role of Wnt signaling in EMT of CRSwNP using a murine nasal polyp (NP) model and human tissues. METHODS: Inflammatory markers and EMT-related molecules were evaluated in NP models using adenomatosis polyposis coli (Apc)Min/+ mice with activated Wnt signaling and NP models treated with Wnt signaling inhibitor, indocyanine green-001 (ICG-001). EMT markers and Wnt signaling-associated mediators were analysed using human sinonasal tissues from control subjects and CRSwNP patients. RESULTS: ApcMin/+ mice-induced NPs exhibited more frequent polypoid lesions and upregulation of Wnt-related molecules, including nuclear ß-catenin, WNT3A and cyclin D1. Markers of EMT were significantly overexpressed in the ApcMin/+ NP mice (p<0.001 for E-cadherin and α-smooth muscle actin), and interleukin (IL)-17A+ cells and neutrophilic infiltration were increased in ApcMin/+ NP mice (p<0.001). Inhibition of Wnt signaling via ICG-001 resulted in significantly decreased nasal polypoid lesions (p<0.001), EMT-related markers (p=0.019 for E-cadherin and p=0.002 for vimentin) and the mRNA levels of IL-4 (p<0.001) and IL-17A (p=0.004) compared with the positive control group. Finally, nuclear ß-catenin (p=0.042) was significantly increased compared with the control, and the expression levels of Wnt ligands and receptors were upregulated in human NP tissues (p=0.045 for WNT3A and p=0.042 for FZD2), suggesting increased Wnt signaling and EMT in CRSwNP. CONCLUSION: Wnt signaling may contribute to the pathogenesis of NPs through EMT. Therefore, inhibition of Wnt signaling may be a potential therapeutic strategy for patients with CRSwNP.


Subject(s)
Epithelial-Mesenchymal Transition/physiology , Nasal Polyps/physiopathology , Rhinitis/physiopathology , Sinusitis/physiopathology , Wnt Signaling Pathway/physiology , Actins/metabolism , Adenomatous Polyposis Coli Protein , Animals , Biomarkers/metabolism , Cadherins/metabolism , Cyclin D1/metabolism , Disease Models, Animal , Humans , Indocyanine Green/pharmacology , Mice , Nasal Polyps/drug therapy , Twist-Related Protein 1/metabolism , Up-Regulation , beta Catenin/metabolism
5.
Clin Exp Otorhinolaryngol ; 13(4): 396-406, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32407614

ABSTRACT

OBJECTIVES: Limited information is available regarding strain-related differences in mouse models of allergic rhinitis induced by Dermatophagoides farinae (Der f1). In this study, we compared differences between two mouse strains and determined the optimal dose of Der f1 for allergic rhinitis mouse models. METHODS: Forty-eight mice were assigned to the following six groups (n=8 per group): group A (control, BALB/c), group B (Der f1-sensitized BALB/c, 25 µg), group C (Der f1-sensitized BALB/c, 100 µg), group D (control, C57BL/6), group E (Der f1-sensitized C57BL/6, 25 µg), and group F (Der f1-sensitized C57BL/6, 100 µg). Allergic inflammation was induced with Der f1 and alum sensitization, followed by an intranasal challenge with Der f1. Rubbing and sneezing scores, eosinophil and neutrophil infiltration, and immunoglobulin, cytokine, and chemokine levels in the nasal mucosa and from splenocyte cultures were assessed. RESULTS: Rubbing and sneezing scores were higher in groups B, C, E, and F than in groups A and D, with a similar pattern in both strains (i.e., group B vs. E and group C vs. F). Serum immunoglobulin levels were significantly elevated compared to the control in groups B and C, but not in groups E and F. Eosinophil and neutrophil infiltration increased (all P<0.05) after the Der f1 challenge (groups B, C, E, and F) compared to the control (groups A and D) in both the BALB/c and C57BL/6 strains, without any significant difference between the two strains (group A vs. D, group B vs. E, and group C vs. F) (P>0.05). BALB/c mice (group B) showed a greater elevation of splenic interleukin (IL)-4 (P<0.01), IL-5 (P<0.01), and IL-6 levels (P<0.05) and nasal IL-4 mRNA levels (P<0.001) than the C57BL/6 mice (group E). Interestingly, mice treated with 100 µg Der f1 showed a weaker allergic response than those treated with 25 µg. CONCLUSION: We found 25 µg to be a more appropriate dose for Der f1 sensitization. BALB/c mice are more biased toward a Th2 response and are a more suitable model for allergic rhinitis than C57BL/6 mice. This study provides information on the appropriate choice of a mouse model for allergic rhinitis.

6.
Allergy Asthma Immunol Res ; 12(3): 507-522, 2020 May.
Article in English | MEDLINE | ID: mdl-32141263

ABSTRACT

PURPOSE: Th17-associated inflammation is increased in chronic rhinosinusitis with nasal polyp (CRSwNP), and is associated with disease severity and steroid resistance. Overexpressed interleukin (IL)-17A affects CRSwNP by tissue remodeling, eosinophilic accumulation, and neutrophilic infiltration. We aimed to identify the role of IL-17A in CRSwNP and to evaluate the effects of anti-IL-17A blocking antibody on nasal polyp (NP) formation using a murine NP model. Moreover, we sought to investigate whether the inhibition of mechanistic target of the rapamycin (mTOR) signal pathway could suppress IL-17A expression and NP formation. METHODS: Human sinonasal tissues from control subjects and patients with chronic rhinosinusitis (CRS) were analyzed using immunohistochemistry (IHC) and immunofluorescence staining. The effects of IL-17A neutralizing antibody and rapamycin were evaluated in a murine NP model. Mouse samples were analyzed using IHC, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. RESULTS: IL-17A⁺ inflammatory cells were significantly increased in number in NP from patients with CRSwNP compared to that in uncinate process tissues from control subjects and patients with CRS without NP or CRSwNP. CD68⁺ M1 macrophages dominantly expressed IL-17A, followed by neutrophils and T helper cells, in NP tissues. Neutralization of IL-17A effectively reduced the number of NPs, inflammatory cytokines, and IL-17A-producing cells, including M1 macrophages. Inhibition of IL-17A via the mTOR pathway using rapamycin also attenuated NP formation and inflammation in the murine NP model. CONCLUSIONS: IL-17A possibly plays a role in the pathogenesis of CRSwNP, the major cellular source being M1 macrophage in NP tissues. Targeting IL-17A directly or indirectly may be an effective therapeutic strategy for CRSwNP.

7.
Elife ; 92020 02 04.
Article in English | MEDLINE | ID: mdl-32014112

ABSTRACT

Cyclic AMP (cAMP) is involved in many biological processes but little is known regarding its role in shaping immunity. Here we show that cAMP-PKA-CREB signaling (a pattern recognition receptor [PRR]-independent mechanism) regulates conventional type-2 Dendritic Cells (cDC2s) in mice and reprograms their Th17-inducing properties via repression of IRF4 and KLF4, transcription factors essential for cDC2-mediated Th2 induction. In mice, genetic loss of IRF4 phenocopies the effects of cAMP on Th17 induction and restoration of IRF4 prevents the cAMP effect. Moreover, curdlan, a PRR-dependent microbial product, activates CREB and represses IRF4 and KLF4, resulting in a pro-Th17 phenotype of cDC2s. These in vitro and in vivo results define a novel signaling pathway by which cDC2s display plasticity and provide a new molecular basis for the classification of novel cDC2 and cDC17 subsets. The findings also reveal that repressing IRF4 and KLF4 pathway can be harnessed for immuno-regulation.


Subject(s)
Interferon Regulatory Factors , Receptors, Pattern Recognition , Signal Transduction/immunology , Th17 Cells , Th2 Cells , Animals , Cell Line, Tumor , Cyclic AMP/immunology , Cyclic AMP/metabolism , Cytokines , Dendritic Cells/immunology , Dendritic Cells/metabolism , Humans , Interferon Regulatory Factors/antagonists & inhibitors , Interferon Regulatory Factors/immunology , Interferon Regulatory Factors/metabolism , Kruppel-Like Factor 4 , Mice , Receptors, Pattern Recognition/immunology , Receptors, Pattern Recognition/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism , Th2 Cells/immunology , Th2 Cells/metabolism
8.
Clin Exp Otorhinolaryngol ; 11(2): 146-150, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29665628

ABSTRACT

OBJECTIVES: The post-tonsillectomy pain and post-tonsillectomy hemorrhage are the two main problems after tonsillectomy. The aim of this study was to investigate the beneficial effects of water soluble ethanol extract propolis on post-tonsillectomy patient. METHODS: One hundred and thirty patients who underwent tonsillectomy or adenotonsillectomy were randomly divided into the control and propolis groups, each including 65 patients. The propolis group was applied with propolis orally immediately after surgery and by gargle. The pain scores were assessed on post-tonsillectomy 0, 1st, 2nd, 3rd, and 7th-10th day using a visual analogue scale score. Postoperative wound healing was evaluated by scoring pinkish membrane of tonsillar fossae on postoperative days 3 and 7-10. The incidence of post-tonsillectomy bleeding was examined in each group. RESULTS: Post-tonsillectomy pain was significantly less in propolis group compared to control group on postoperative days 3 and 7-10. Post-tonsillectomy hemorrhage was significantly less in the propolis group compared to the control group (P<0.05). The wound healing was significantly better in the propolis group compared to the control group on postoperative day 7-10 (P=0.002). CONCLUSION: Applying the propolis to post-tonsillectomy wound showed beneficial effect of reducing postoperative pain, preventing hemorrhage, and accelerating of wound healing of tonsillar fossae.

9.
Clin Exp Otorhinolaryngol ; 11(1): 52-57, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28758381

ABSTRACT

OBJECTIVES: It is well known that allergic rhinitis (AR) has positive association with adenotonsillectomy. However, the impact of AR on symptom improvement after adenotonsillectomy is not well documented. Hence, we aimed to evaluate the effect of AR on the symptom improvement after adenotonsillectomy between AR and nonallergic patients. METHODS: A retrospective analysis was performed on 250 pediatric patients younger than 10 years old who received adenotonsillectomy from June 2009 to June 2014 in a tertiary referral hospital. All patients underwent skin prick test or multiple allergen simultaneous test (MAST) before surgery and classified into AR group and control group. Obstructive and rhinitis symptoms including snoring, mouth breathing, nasal obstruction, rhinorrhea, itching, and sneezing were evaluated before and 1 year after surgery using questionnaire and telephone survey. RESULTS: AR group was 131 and control group was 119, showing higher prevalence (52.4%) of AR among adenotonsillectomized patients. Both groups showed dramatic improvement of symptoms such as snoring and mouth breathing after surgery (all P<0.05). However, AR group showed significantly less improvement than control group in snoring, mouth breathing, nasal obstruction, and rhinorrhea (all P<0.05). Multivariate analysis showed that preoperative mouth breathing and snoring were dependent on tonsil grade and postoperative symptoms were mainly dependent on presence of AR. Nasal obstruction was dependent on tonsil grade and presence of AR preoperatively and presence of AR postoperatively. These suggest the importance of AR as a risk factor for mouth breathing, snoring, and nasal obstruction. CONCLUSION: AR has positive association with adenotonsillectomy and not only allergic symptoms but also obstructive symptoms such as snoring and mouth breathing improved less in AR group than control group. Hence, patients with AR should be monitored for long-term basis and more carefully after adenotonsillectomy.

10.
Mediators Inflamm ; 2017: 3908049, 2017.
Article in English | MEDLINE | ID: mdl-28912627

ABSTRACT

BACKGROUND AND PURPOSE: When house dust mite (HDM), a common allergen, comes into the mucosal membrane, it may stimulate innate immunity. However, the precise role of interleukin- (IL-) 25 in the development of HDM-induced nasal allergic inflammation is still unclear. Therefore, we investigated the role of IL-25 in allergic rhinitis (AR) patients sensitized to HDM. METHODS: To confirm the production of IL-25 in human nasal epithelial cells (HNECs), we stimulated HNECs. IL-25 expression in the nasal mucosa from control, non-AR (NAR) patients, and HDM-sensitized AR patients was assessed using immunohistochemistry, and quantitative reverse transcription PCR. Correlations between IL-25 and other inflammatory markers were explored. RESULTS: An in vitro study showed significantly elevated concentrations of IL-25 in the HNEC samples with highest doses of HDM. Nasal tissues from AR patients sensitized to HDM showed significantly higher IL-25 expression, compared to those from the control or NAR patients. Moreover, the expression of IL-25 in nasal tissues from AR patients sensitized to HDM was positively associated with Th2 markers, such as ECP and GATA3. CONCLUSIONS: IL-25 expression increased with high-dose HDM stimulation and was related to Th2 markers. Therefore, IL-25 neutralization might offer a new strategy for treating patients with HDM-sensitized AR.


Subject(s)
Interleukin-17/metabolism , Pyroglyphidae/immunology , Rhinitis, Allergic/immunology , Rhinitis, Allergic/metabolism , Animals , Cells, Cultured , Female , Humans , Immunohistochemistry , Interleukin-17/genetics , Male , Reverse Transcriptase Polymerase Chain Reaction
11.
Clin Exp Otorhinolaryngol ; 9(2): 143-9, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27090275

ABSTRACT

OBJECTIVES: Postoperative bleeding and adhesion formation are the two most common complications after endoscopic sinus surgery (ESS). The former sometimes can be life threatening and the latter is the most common reason requiring revision surgery. This study was designed to evaluate the effect of newly developed chitosan gel (8% carboxymethyl chitosan, Surgi shield) on hemostasis and wound healing after ESS. METHODS: A prospective, randomized, double-blind controlled trial was conducted in 33 patients undergoing symmetric ESS. At the conclusion of the operation, Surgi shield was randomly applied on one side of the nasal cavity, with the opposite side acting as control and the bleeding quantity of the surgical field was evaluated every 2 minutes. And then, Merocel was placed in the ethmoidectomized areas of the both sides. Five milliliters of Surgi shield was applied to the Merocel of intervention side and saline was applied to the other side. Merocel in both nasal cavities was removed and 5 mL of Surgi shield was applied again to the intervention side on the second day after surgery. The nasal cavity was examined using a nasal endoscope and the degree of adhesion, crusting, mucosal edema, infection, and granulations were graded at 1, 2, and 4 weeks after surgery. RESULTS: Complete hemostasis was rapidly achieved in the Surgi shield applied side compared with the control side at 2, 4, 6, 8, and 10 minutes after application of Surgi shield (P=0.007, P=0.004, P<0.001, P=0.001, and P<0.001, respectively). There were significantly less adhesions on the Surgi shield applied side at postoperative 1, 2, and 4 weeks (P=0.001, P<0.001, and P<0.001, respectively). The degree of mucosal edema, infection, crusting, or granulation formation assessed by the endoscopic features in the Surgi shield applied side was not significantly different from that of the control side (P>0.05). No adverse effects were noted in the patient series. CONCLUSION: Surgi shield containing chitosan can be used safely to achieve rapid hemostasis immediately after ESS and to prevent adhesion formation.

12.
Oncotarget ; 7(1): 148-60, 2016 Jan 05.
Article in English | MEDLINE | ID: mdl-26700618

ABSTRACT

Transient receptor potential vanilloid 1 (TRPV1), which has been identified as a molecular target for the activation of sensory neurons by various painful stimuli, was reported to regulate the signaling and activation of CD4+ T cells. However, the role of TRPV1 in CD4+ T cell in allergic rhinitis remains poorly understood. In this study, TRPV1 expression was localized in CD4+ T cells. Both knockout and chemical inhibition of TRPV1 suppressed Th2/Th17 cytokine production in CD4 T cells and Jurkat T cells, respectively, and can suppress T cell receptor signaling pathways including NF-κB, MAP kinase, and NFAT. In TRPV1 knockout allergic rhinitis (AR) mice, eosinophil infiltration, Th2/Th17 cytokines in the nasal mucosa, and total and ova-specific IgE levels in serum decreased, compared with wild-type AR mice. The TRPV1 antagonists, BCTC or theobromine, showed similar inhibitory immunologic effects on AR mice models. In addition, the number of TRPV1+/CD4+ inflammatory cells increased in the nasal mucosa of patients with AR, compared with that of control subjects. Thus, TRPV1 activation on CD4+ T cells is involved in T cell receptor signaling, and it could be a novel therapeutic target in AR.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Inflammation/immunology , Rhinitis, Allergic/immunology , TRPV Cation Channels/immunology , Adolescent , Adult , Animals , Blotting, Western , CD4-Positive T-Lymphocytes/metabolism , Cytokines/genetics , Cytokines/immunology , Cytokines/metabolism , Eosinophils/immunology , Eosinophils/metabolism , Female , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Immunohistochemistry , Inflammation/genetics , Inflammation/metabolism , Jurkat Cells , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , Nasal Mucosa/immunology , Nasal Mucosa/metabolism , Ovalbumin/immunology , Reverse Transcriptase Polymerase Chain Reaction , Rhinitis, Allergic/genetics , Rhinitis, Allergic/metabolism , TRPV Cation Channels/genetics , TRPV Cation Channels/metabolism , Young Adult
13.
Int Forum Allergy Rhinol ; 5(10): 950-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26033543

ABSTRACT

BACKGROUND: The aim of this work was to evaluate factors that influence local recurrence and survival after surgical resection of sinonasal malignant melanoma, using a large population-based multicenter study in Korea. METHODS: Retrospective analysis was performed for 155 newly diagnosed sinonasal malignant melanoma patients gathered from 15 university hospitals throughout Korea. Demographic data, tumor characteristics, surgical approach, adjuvant treatment, recurrence, and outcomes were analyzed. RESULTS: Three-year and 5-year overall survival rates were 48.8% and 40.1%, respectively. Local recurrence rate was 46.6%, with a mean recurrence time of 15.5 months. On multivariate analysis, patients who underwent surgery that included an endoscopic approach showed decreased local recurrence rate (p = 0.042) and increased survival rate (hazard ratio [HR], 1.702; 95% confidence interval [CI], 1.007 to 2.875; p = 0.047) compared to those who underwent an external approach. Patients with postoperative radiotherapy showed a decreased local recurrence rate (p = 0.001), but without impact on survival rate. Male gender, tumor beyond the nasal cavity, and presence of distant metastasis were associated with poor survival. CONCLUSION: An endoscopic-including surgical approach was associated with improved local control and survival in sinonasal malignant melanoma patients. Postoperative radiotherapy helped increase the local control rate.


Subject(s)
Melanoma/diagnosis , Nose Neoplasms/diagnosis , Population Groups , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Korea , Male , Melanoma/mortality , Melanoma/surgery , Middle Aged , Neoplasm Recurrence, Local , Nose Neoplasms/mortality , Nose Neoplasms/surgery , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome
14.
Am J Rhinol Allergy ; 29(4): 262-7, 2015.
Article in English | MEDLINE | ID: mdl-26085003

ABSTRACT

BACKGROUND: Although several studies have claimed that mesenchymal stem cells (MSC) derived from human tissues can ameliorate allergic airway inflammation, the immunomodulatory mechanism of MSCs remains unclear. OBJECTIVE: We aimed to determine the effects and the underlying mechanism of tonsil-derived MSCs (T-MSC) on allergic inflammation compared with adipose tissue-derived stem cells (ASC) in a mouse model of allergic rhinitis (AR). METHODS: MSCs were isolated from human palatine tonsil (T-MSC) and the surface markers were analyzed. The effect of T-MSCs was evaluated in 24 BALB/c mice that were randomly divided into four groups (negative control group, positive control group, T-MSC group, and ASC group). MSCs were administered intravenously to ovalbumin (OVA) sensitized mice (T-MSC and ASC groups) on days 18 to 23, and subsequent OVA challenge was conducted daily from days 24 to 28. Several parameters of allergic inflammation were assessed. RESULTS: T-MSC and ASC had similar characteristics in surface markers. Intravenous injection of T-MSC significantly reduced allergic symptoms, eosinophil infiltration, serum total, and OVA-specific immunoglobulin E (IgE), and the nasal and systemic T-helper (Th) 2 cytokine profile. Further analysis revealed that nasal innate cytokines, such as interleukin (IL) 25 and IL-33, and chemokines, such as CCL11, CCL24, induction was suppressed in T-MSCs injected groups, which explained their underlying mechanism. In addition, the T-MSC group had more inhibition of allergic inflammation than did the ASC group, which might be attributed to the more proliferative activity of T-MSC. CONCLUSION: Administration of T-MSC effectively reduced allergic symptoms and inflammatory parameters in the mouse model of AR. T-MSC treatment reduced Th2 cytokines and OVA-specific IgE secretion from B cells. In addition, innate cytokine (IL-25 and IL-33) expression and eotaxin messenger RNA expression was inhibited in the nasal mucosa, which is suggestive of the mechanism of reduced allergic inflammation. Therefore, T-MSC treatment is potentially an alternative therapeutic modality in AR.


Subject(s)
Immunomodulation , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/immunology , Rhinitis, Allergic/surgery , Adipose Tissue/immunology , Animals , Disease Models, Animal , Humans , Mice , Mice, Inbred BALB C , Nasal Mucosa , Palatine Tonsil/immunology , Random Allocation , Rhinitis, Allergic/immunology , Treatment Outcome
15.
Am J Rhinol Allergy ; 28(3): 208-14, 2014.
Article in English | MEDLINE | ID: mdl-24980232

ABSTRACT

BACKGROUND: Exposure to cigarette smoking (CS) is a major risk factor for airway inflammation. However, little is known about the effects of CS exposure on eosinophilic rhinosinusitis with nasal polyps (ERSwNPs). Histopathological and molecular studies were performed to investigate its effects using a murine model of ERSwNPs. METHODS: Mice were assigned to one of the following four groups (n = 8 for each group): control group, CS exposure (CS group), ERSwNP (ERS group), and ERSwNPs exposed to CS (ERS + CS group). Histopathological changes were investigated using various stains, including hematoxylin and eosin for inflammation and polyp-like lesions, Sirius red for eosinophils, toluidine blue for mast cells, Alcian blue for goblet cells, and Masson's trichrome stain for collagen fibers. mRNA expression of cytokines from nasal mucosae was measured. Serum IgE and systemic cytokine levels were measured by enzyme-linked immunosorbent assays. The expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF) 1-alpha was evaluated by immunohistochemical staining. RESULTS: The ERS + CS group showed more severe symptoms, increased the number of polyp-like lesions, infiltration of eosinophils, goblet cell hyperplasia, and subepithelial fibrosis, compared with the ERS group. Additionally, mRNA expressions of IL-4 and IL-17A were up-regulated in ERS + CS group and higher levels of IL-4, IL-6, IL-17A, and interferon gamma from splenocytes were observed significantly in the ERS + CS group compared with the ERS group. In the ERSwNP murine model, exposure to CS enhanced the expression of VEGF and HIF-1-alpha in nasal epithelial cells. CONCLUSION: Chronic exposure to CS aggravated eosinophilic inflammation and promoted airway remodeling and nasal polyp formation in a murine model of ERSwNPs. The underlying mechanism might involve up-regulated expression of VEGF and HIF-1-alpha.


Subject(s)
Eosinophils/immunology , Goblet Cells/pathology , Nasal Mucosa/immunology , Nasal Polyps/immunology , Smoking/adverse effects , Airway Remodeling , Animals , Cytokines/metabolism , Disease Models, Animal , Fibrosis , Humans , Hyperplasia , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Immunoglobulin E/blood , Mice , Mice, Inbred BALB C , Nasal Polyps/pathology , Vascular Endothelial Growth Factor A/metabolism
16.
Eur Arch Otorhinolaryngol ; 271(6): 1573-80, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24132655

ABSTRACT

Although the regeneration process for injured cartilage requires an intact perichondrium, few studies have addressed the importance of the intact perichondrial layer in the regeneration of damaged cartilage. In this study, we evaluated the role of the perichondrium on regenerative activities in injured cartilage according to different degrees of perichondrial injury. Auricular cartilage harvested from six New Zealand white rabbits was irradiated with a 1,460-nm diode laser at two different power settings (0.3 or 0.5 W). Irradiated cartilage was reimplanted into a subperichondrial pocket under three different conditions: non-injured perichondrium (NPI), unilaterally injured perichondrium (UPI), or bilaterally injured perichondrium (BPI). Rabbits were sacrificed at 1, 2, and 4 weeks after reimplantation and the auricular cartilage was reharvested. A histopathological study using hematoxylin and eosin staining, a live/dead viability assay, and immunohistochemical staining for proliferating cell nuclear antigen were performed to evaluate structural changes and regenerative and proliferative activities of the injured chondrocytes. A modified array and restored boundary of chondrocytes were observed in the NPI and UPI groups. Regeneration of chondrocytes was prominent in the NPI and UPI groups, but was not observed in the BPI group. Proliferative activity of chondrocytes was observed only when the perichondrium was preserved in the NPI and UPI groups. In contrast, proliferative activity was not observed until 4 weeks in the BPI group. The degree of perichondrial injury affected proliferation and regeneration in injured elastic cartilage. In the case of unilateral perichondrial injury, the surgeon should be careful to avoid damaging the other side of the perichondrium, because at least a unilateral perichondrial layer is needed for the regeneration of elastic cartilage.


Subject(s)
Cell Proliferation/physiology , Chondrocytes/physiology , Ear Cartilage/physiology , Regeneration/physiology , Animals , Cell Survival , Chondrocytes/cytology , Chondrocytes/pathology , Ear Cartilage/cytology , Ear Cartilage/injuries , Ear Cartilage/pathology , Rabbits , Severity of Illness Index
17.
Am J Rhinol Allergy ; 27(6): e174-7, 2013.
Article in English | MEDLINE | ID: mdl-24274210

ABSTRACT

BACKGROUND: Nasal packing is usually performed to control bleeding after endoscopic sinus surgery (ESS). Although new packing materials have been developed, they still cause pain. This study was designed to evaluate the effect of lidocaine-soaked packs on pain after ESS. METHODS: A prospective, randomized, double-blind controlled trial was conducted in 63 patients with CRS undergoing ESS. At the conclusion of the operation, 2% lidocaine-soaked biodegradable synthetic polyurethane foam and saline-soaked polyurethane foam were inserted in both nasal cavities of 31 patients and 32 control patients, respectively. The same lidocaine or saline was reapplied into the nasal packs at postoperative 8 hours. Pain was evaluated using a visual analog scale at postoperative 1, 4, 8, 16, 20, and 24 hour(s). The number of gauze that cleaned the blood around the nose was counted. Heart rate, rhythm, and blood pressures were checked preoperatively and postoperatively to evaluate the influence of lidocaine on vital signs. RESULTS: Postoperative pain decreased in lidocaine group at all of the postoperative time periods (p < 0.05). Lidocaine reduced postoperative bleeding at postoperative 8 and 24 hours. Changes of blood pressure from preoperative values in the lidocaine group were not different from those in the control group (p > 0.05). Heart rate in the lidocaine group was more stable than that in the control group (p < 0.05). CONCLUSION: Lidocaine-soaked packs significantly reduced postoperative pain without serious changes on vital sign. These findings suggest that topical lidocaine application to nasal packs could be a useful method to reduce pain during the early postoperative period after ESS.


Subject(s)
Endoscopy/methods , Lidocaine/administration & dosage , Pain, Postoperative/prevention & control , Paranasal Sinuses/surgery , Postoperative Hemorrhage/prevention & control , Adult , Double-Blind Method , Female , Humans , Male , Middle Aged , Prospective Studies
18.
Clin Exp Otorhinolaryngol ; 6(3): 187-90, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24069524

ABSTRACT

Obstructive sleep apnea (OSA) is a common disorder. It usually results from the structural compromise of the upper airway. In patients with OSA, the obstruction predominantly occurs along the pharyngeal airway, and also a variety of tumors have been reported to cause such a condition. We present here the case of a thyroglossal duct cyst causing OSA in adult. This case demonstrates that thyroglossal duct cyst or some kind of mass lesions in the airway lesions should be considered in the differential diagnosis of OSA patients.

19.
Asia Pac Allergy ; 3(3): 186-93, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23956965

ABSTRACT

BACKGROUND: Th2 cells are crucially important in allergic disease and the possible involvement of Treg and Th17 cells has not been clearly identified. OBJECTIVE: To identify the mRNA expression of T cell transcription factors in nasal mucosa in patients with allergic rhinitis (AR) and to reveal their correlations with clinical features. METHODS: Eighteen patients with AR and 12 controls with turbinate hypertrophy were included. mRNA expression of the following transcriptional factors in nasal mucosa were measured by quantitative polymerase chain reaction; T-bet (Th1), GATA3 (Th2), retinoic acid-related orphan receptor C (RORC; Th17), and forkhead box P3 (Foxp3; Treg). mRNA expression was compared among groups and correlation between mRNA expression level and clinical features (rhinitis symptoms, eosinophil count, and IgE) were also investigated. RESULTS: GATA3 and RORC were significantly increased and Foxp3 was significantly decreased in the AR group. Moderate-to-severe AR group also had increased expression of GATA3 and RORC than mild AR group, suggesting severity of AR influence expression of transcription factors. Correlation analysis showed that none of these transcription factors were associated with severity of clinical symptoms, eosinophil counts and skin prick test severity and that IgE level was significantly correlated with expression level of GATA3 and RORC, suggesting an association of IgE production with Th2 and Th17 cells. CONCLUSION: Increased mRNA expression of GATA3 (Th2), increased expression of RORC and decreased expression of Foxp3 may be important in pathogenesis of AR. GATA3 and RORC may be closed related with IgE level.

20.
Clin Exp Otorhinolaryngol ; 6(2): 82-9, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23799165

ABSTRACT

OBJECTIVES: Cartilage reshaping by laser irradiation is used to correct septal and auricular cartilage deformities. Chondrocyte viability following laser irradiation and reshaping has been well established. However, the regeneration process of chondrocyte after laser irradiation has not been revealed yet. The aims of this study were to determine the mechanism of cartilaginous thermal injury and the regenerative process of damaged cartilage following laser irradiation. METHODS: Laser irradiation was performed on human septal cartilage and rabbit auricular cartilage using a 1,460-nm diode laser. We observed change in the shape of cartilage and evaluated the extent of cartilage injury using live/dead cell assay via confocal microscopy. Hoechst and propidium iodide (PI) staining was used to evaluate the mechanism of chondrocyte injury after laser irradiation. To evaluate the regeneration of cartilage, laser irradiated cartilages were reimplanted into a subperichondrial pocket and were harvested at 1, 2, and 4 weeks after reimplantation for viability assessment and histologic examination. RESULTS: Laser irradiation using a 1,460-nm diode laser produced a marked shape change in both human septal and rabbit auricular cartilages. Thermal damage on cartilage was correlated with the exposure time and the laser power. Hoechst and PI staining showed that chondrocyte death by laser irradiation was due to mainly necrosis, rather than apoptosis. In lower power treatment group (0.3 W and 0.5 W), all the chondrocytes regenerated within 4 weeks, however, in 1 W treatment group, chondrocytes could not regenerate until 4 weeks. CONCLUSION: Reshaping of cartilage using 1,460 nm diode laser was attained concurrently with the thermal injury to the chondrocytes. The extent of thermal damage on chondrocytes was dependent on the exposure time and the laser power and the damaged chondrocytes irradiated with lower level of laser power could be regenerated after reimplantation into subperichondrial pocket.

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