Histological Changes In Nasal Mucosa Research Articles

Human placental extract regulates polarization of macrophages via IRGM/NLRP3 in allergic rhinitis

Allergic rhinitis (AR) is globally prevalent and its pathogenesis remains unclear. Alternative activation of macrophages is suggested in AR and thought to be involved in natural immunoregulatory processes in AR. Aberrant activation of Nod-like receptor protein 3 (NLRP3) inflammasome is linked with AR. Human placenta extract (HPE) is widely used in clinics due to its multiple therapeutic potential carried by diverse bioactive molecules in it. We aim to investigate the effect of HPE on AR and the possible underlying mechanism. Ovalbumin (OVA)-induced AR rat model was set up and treated by HPE or cetirizine. General manifestation of AR was evaluated along with the histological and biochemical analysis performed on rat nasal mucosa. A proteomic analysis was performed on AR rat mucosa. Mouse alveolar macrophages (MH-S cells) were cultured under OVA stimulation to investigate the regulation of macrophages polarization. The morphological changes and the expression of NLRP3 inflammasome and immunity-related GTPase M (IRGM) in nasal mucosa as well as in MH-S cells were evaluated respectively. The results of our study showed the general manifestation of AR along with the histological changes in nasal mucosa of AR rats were improved by HPE. HPE suppresses NLRP3 inflammasome and the decline of IRGM in AR rats and MH-S cells. HPE regulates macrophage polarization through IRGM/NLRP3. We demonstrated that HPE had protection for AR and the protection is achieved partly through suppressing M1 while promoting M2, the process which is mediated by IRGM via inhibiting NLRP3 inflammasome in AR.

Knockdown of Cadherin 26 Prevents the Inflammatory Responses of Allergic Rhinitis.

Allergic rhinitis (AR) is an inflammatory autoimmune disease with disorder of the nasal mucosa. Cadherin 26 (CDH26), an alpha integrin-binding epithelial receptor, is regulated during allergic inflammation. This study aimed to investigate whether CDH26 contributes to the severity of AR. In vivo and in vitro. We investigated the effects of CDH26 knockdown by lentivirus (LV)-mediated shRNA on ovalbumin (OVA)-induced AR mice and IL-13-stimulated human nasal epithelial cells (NECs). CDH26 mRNA and protein expression was significantly increased in the nasal mucosa of AR patients and mice. Intranasal instillation of LV-shCDH26 alleviated allergic symptoms and decreased the histological changes of nasal mucosa in AR mice. Furthermore, the serum levels of OVA-specific IgE, IgG, pro-inflammatory factors IL-25, IL-33, and TSLP were decreased in AR mice with CDH26 knockdown. With regard to AR-induced Th2 inflammation, LV-shCDH26 intervention effectively decreased the distribution of CD4+ /GATA3+ Th2 cells, and the mRNA expression of IL-4, IL-5, and IL-13 in the nasal mucosa. CDH26 knockdown down-regulated the expression of β-catenin but not for E-cadherin and ZO-1 in nasal mucosa induced by AR. In vitro, CDH26 knockdown inhibited the protein expression of TSLP, GM-CSF and eotaxin in NECs, and CDH26 overexpression remarkably promoted the production of these inflammatory factors in IL-13-induced NECs. CDH26 knockdown attenuates the AR-induced inflammatory response both in vivo and in vitro. NA Laryngoscope, 133:1558-1567, 2023.

Tussilagone inhibits allergic responses in OVA-induced allergic rhinitis guinea pigs and IgE-stimulated RBL-2H3 cells

Farfarae Flos is the dried flower buds of Tussilago farfara L. which is widely used to treat allergic and inflammatory diseases in Chinese folk. Tussilagone (TSL), a sesquiterpene compound purified from Farfarae Flos, has been confirmed the main active component in the plant. However, its anti-allergic activity hasn't been reported yet. The purpose of this study is to investigate the anti-allergic effect of TSL in ovalbumin (OVA)-induced allergic rhinitis (AR) guinea pigs and immunoglobulin E (IgE)-stimulated RBL-2H3 cells. The AR symptoms such as nasal scratching, sneezing and runny nose were scored and the histological changes of nasal mucosa were observed by H&E staining. The levels of histamine, OVA-specific IgE, IL-6 and TNF-α in the serum were measured by ELISA. In IgE-stimulated RBL-2H3 cells, the phosphoryration of Lyn, Syk, Akt, NF-κB p65, ERK and p38 MAPK were investigated by western blot analysis. The results showed that intraperitoneal injection of TSL at doses of 25 and 50 mg/kg significantly alleviated the allergic symptoms and the histological changes of nasal mucosa in OVA-induced allergic rhinitis guinea pigs. Moreover, the levels of histamine, IgE and IL-6 in the serum decreased significantly (p < .05). In vitro, TSL suppressed the phosphorylation of Lyn, Syk, Akt, NF-κB p65, ERK and p38 MAPK in IgE-stimulated RBL-2H3 cells. These results indicate TSL has therapeutic effect on allergic rhinitis in guinea pigs. The anti-allergic mechanism may be through the inhibition of allergic and inflammatory related pathways in mast cells.

Ethno-medicinal study of Artemisia ordosica Krasch. (traditional Chinese/Mongolian medicine) extracts for the treatment of allergic rhinitis and nasosinusitis.

Artemisia ordosica Krasch. (AOK) has been used for rheumatic arthritis, cold headache, sore throat, etc. in traditional Chinese/Mongolian medicine and is used for nasosinusitis by local Mongolian "barefoot" doctors. Up to now, their mechanisms are still unclear. To evaluate the in vivo anti-inflammatory and allergic rhinitis (AR) alleviating effect as well as in vitro antimicrobial activities of AOK extracts to verify its ethno-medicinal claims. Crude extracts (methanol/95%-ethanol/ethyl acetate) of AOK root/stem/leaf and fractions (petroleum ether/ethyl acetate/n-butanol/aqueous) of AOK root extract were prepared. Xylene-induced ear swelling model in mouse and ovalbumin (OVA)-induced AR model in guinea pig were established. Ear swelling degrees of mice were measured. The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR. The serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1 were measured by ELISA assay. The histological changes of nasal mucosa were investigated by light microscope after H&E staining. Antimicrobial activities of AOK extracts were also tested. LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism. In ear-swelling model, extract (100.00 mg/kg) from the ethyl acetate layer of 95% ethanol (100.00 mg/kg) showed better swelling inhibition in mice than positive control (dexamethasone, 191.91 mg/kg). In AR model, extract from the ethyl acetate layer of 95% ethanol significantly alleviated the AR symptoms in guinea pigs, decreased the serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1, and reduced the infiltration of eosinophil in nasal mucosa. For Staphylococcus aureus, the ethyl acetate extract of AOK stem showed the highest inhibition (MIC=1.25 mg/mL), for Escherichia coli, n-butanol layer of 95% ethanol extract of AOK root showed the highest inhibition (MIC=15.00 mg/mL), for Candida glabrata, 95%-ethyl acetate extract of AOK leaf showed the best inhibition (MIC=0.064 mg/mL), while ethyl acetate and n-butanol layers showed similar inhibition on MRSA (MIC=7.50 mg/mL). LC-MS/MS characterization showed that dicaffeoylquinic acids account for more than 30% of ethyl acetate layer of AOK extract. Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes. Extracts from AOK had interesting anti-inflammatory activity in mice, alleviating effect against OVA-induced AR in guinea pigs, and antimicrobial activities in vitro, which support the ethno-medicinal use of it. The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well. These findings highlighted the importance of natural product chemistry study of AOK.

Expression of LC3 and ECP in allergic rhinitis and their significance

Objective:To investigate the expression of microtubuleassociated protein 1 light chain 3 beta(LC3) and eosinophil cationic protein in allergic rhinitis(AR) for further understanding of the pathogenesis of AR. Method: Twenty cases of normal nasal mucosa and 20 cases of AR nasal mucosa were collected. Histological changes of nasal mucosa were examined by hematoxylin and eosin(HE) staining. The expression of LC3 and ECP were measured by immunohistochemistry(IHC) and Western Blot(WB). Result: The tissue samples demonstrated a large number of eosinophils and lymphocytes infiltration in AR. IHC revealed that LC3 and ECP expression were higher in AR than in normal nasal mucosa(P<0.05). WB also showed that the relative expression levels of protein expression of LC3 and ECP were greater in AR than in controls. The expression level of LC3 was positively correlated with that of ECP protein in AR. Conclusion: LC3 and ECP were upregulated and positively correlated in AR, indicating that autophagy plays an important role in the toxicity of allergic rhinitis , which provides theoretical basis for the precise treatment of AR.

Inhibitory effect of baicalin on allergic response in ovalbumin-induced allergic rhinitis guinea pigs and lipopolysaccharide-stimulated human mast cells.

Baicalin, a flavonoid compound purified from the dry roots of Scutellaria baicalensis Georgi, has generally been used for the treatment of various allergic diseases. However, there is little information about the anti-inflammatory effects of baicalin for allergic rhinitis. This study aims to investigate the anti-allergic effect of baicalin on allergic response in ovalbumin (OVA)-induced allergic rhinitis guinea pigs and lipopolysaccharide (LPS)-stimulated human mast cells. Using in vivo models, we evaluated the effect of baicalin on allergic rhinitis symptoms via recording the number of nasal rubs and sneezes. The levels of histamine, OVA-specific immunoglobulin E(IgE), eosinophil cationic protein (ECP) and inflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The histological changes of nasal mucosa were observed by light microscope after HE staining. In vitro, the release of histamine and β-hexosaminidase of compound 48/80-induced human mast cells were measured by ELISA and PNP-NAG colorimetry, respectively. The productions of inflammatory cytokines of LPS-stimulated human mast cells were determined using ELISA. Western blot was used to test the protein expression of JAK2, p-JAK2, STAT5, p-STAT5, IKKβ, p-IKKβ, IκBα, p-IκBα and NF-κB (p65) of LPS-stimulated human mast cells. The oral administration of baicalin at doses of 50 and 200mg/kg improved allergic rhinitis symptoms and the histological changes of nasal mucosa and decreased the serum levels of histamine, ECP, interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α and OVA-specific IgE in OVA-induced allergic rhinitis guinea pigs. In vitro, baicalin suppressed the release of histamine and β-hexosaminidase in compound 48/80-induced human mast cells. In addition, baicalin also inhibited the productions of inflammatory cytokines such as IL-1β, IL-6, IL-8 and TNF-α and suppressed the phosphorylation of JAK2, STAT5, IKKβ, IκBα and the nuclear translocation of NF-κB (p65) subunit in LPS-stimulated human mast cells. These results suggest that baicalin can effectively prevent allergic response in OVA-induced allergic rhinitis guinea pigs and inhibit inflammatory response via blocking JAK2-STAT5 and NF-κB signaling pathways in LPS-stimulated human mast cells. Considered together,the results show that baicalin may be a useful drug in the treatment of allergic rhinitis.

Transdifferentiation of Clara Cell 10-kDa Protein Secreting Cells in Experimental Allergic Rhinitis

The reasons for the down-regulated Clara cell 10-kDa protein (CC10) expression in allergic rhinitis (AR) are unclear and the airway remodeling in AR has received little attention. This study explores epithelium remodeling and the change of CC10 secreting cells in AR by using a murine model. AR murine models were established by ovalbumin sensitization and challenge. In some mice, dexamethasone was given before each challenge. Histological changes of nasal mucosa were examined by means of hematoxylin and eosin and periodic acid-Schiff staining. CC10 and trefoil factor family (TFF) 1 expression were evaluated by immunohistochemistry. In AR mice, both in turbinate and in septal mucosa, total cell number and the number of basal cells did not change; however, the number of dome-shaped cells decreased and the number of ciliated and goblet cells increased in turbinate mucosa, and the number of ciliated cells decreased and the number of goblet cells increased in septal mucosa. In turbinate mucosa, the number of CC10(+) cells (mainly dome-shaped cells) decreased whereas the number of TFF1(+) cells (mainly ciliated cells) increased. In septal mucosa, the number of CC10(+) and TFF1(+) cells (mainly ciliated cells) decreased simultaneously. Intermediate phenotypic goblet cells could express CC10 and TFF1. CC10 and TFF1 could be localized in the same cells. Dexamethasone reversed the changes of epithelium significantly. Allergen exposure leads to a possible transdifferentiation of CC10 secreting cells into TFF1 secreting cells and/or goblet cells in upper airways. Nasal turbinate and septal epithelium display different patterns of transdifferentiation.

The Influence of the Sick House Syndrome on Nasal Mucosa and Nasal Symptoms

Background and ObjectivesZZConcerns about the quality of indoor air have increased recently. However, there has not been any significant research conducted concerning the patterns of histologic and organic changes induced in humans by indoor air pollution. The aim of the study is to investigate the organic changes of nasal mucosa and nasal symptoms due to exposed concentrations of indoor air pollution. Subjects and MethodZZWe studied fourteen people from four families, all of whom had plans to move into new apartments. We measured the quantities of indoor air pollution before their move, one week after moving in, and then one month after the move. Other clinical tests such as an acoustic rhinometry, olfactory tests and nasal smears were performed. ResultsZZMean concentrations of Total Volatile Organic Chemicals (TVOCs) and aldehydes showed an increase after moving into the new apartments. Post-move acoustic rhinometry, Connecticut Chemosensory Clinical Research Center (CCCRC) test and endoscopic findings showed a decrease in nasal function and patency. Additionally, in nasal smears, eosinophils with bilobulated nuclei were observed, and eosinophil count showed a pattern of increase. ConclusionZZHigh concentrations of indoor air pollutants could induce organic changes of the nasal cavities and cause the recession of olfactory function. Due to indoor air pollutants, hypersensitivity of nasal mucosa was induced, and histological changes of nasal mucosa as well as hematological changes were observed. These indicate that indoor air pollution impinges on the nasal mucosa and cause nasal symptoms. � Korean J Otorhinolaryngol-Head Neck Surg 2011;54:265-70 Key WordsZZIndoor air pollution ㆍSick building syndrome ㆍAllergic rhinitis.

Anti-allergic effect of Okbyungpoongsan-Hap-Changijasan

Objectives : In this study, we investigated anti-allergic effect of Okbyeongpungsan-Hap-Changijasan (KOB01) in allergic rhinitis(AR) experimental animals and mast cells. Methods : The potential anti-allergic effect of KOB01 was investigated in a rat model of compound 48/80-induced systemic anaphylactic shock and a mouse of ovalbumin(OVA)-induced AR, and human mast cell line, HMC-1 culture. Each animals were divided into four groups: normal, control, KOB01-treated(100 and 200 mg/kg) and anti-histamine drug, dosodium cromoglycate (DSCG)-treated(50 mg/kg). Animals were orally treated with KOB01 and DSCG and intraperitoneally injected with compound 48/80() or sensitized with 0.1% OVA. The mortality and serum histamine levels were measured in compound 48/80-induced anaphylatic rats. The histological changes in nasal mucosa were investigated in OVA-induced AR mice. Also, mast cell degranulation was observed in compound 48/80-stimulated HMC-1 cells. Results : KOB01 increased mortality and significantly decreased serum histamine levels in compound 48/80-induced anaphylatic rats. The abnormal histological changes such as expansion of grandular cells and hypertrophy of epithelium in nasal mucosa of OVA-induced AR mice was improved by KOB01 treatment nearby a normal group. Therefore, KOB01 inhibited compound 48/80-induced degranulation in HMC-1 cells. Conclusions : These results indicate that KOB01 decrease allergic response through suppressing the mast cell activation in AR and suggest a potential role for KOB01 as a source of anti-allergic agents for use in allergic disorders including of AR.