Role of the TSLP–DC–OX40L pathway in asthma pathogenesis and airway inflammation in mice

2018 ◽  
Vol 96 (3) ◽  
pp. 306-316 ◽  
Author(s):  
Shuang Feng ◽  
Li Zhang ◽  
Xu-Hua Bian ◽  
Ying Luo ◽  
Guang-Hui Qin ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Immunoglobulin E ◽  
Serum Levels ◽  
Lavage Fluid ◽  
Treg Cells ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Total Serum ◽  
Ifn Γ ◽  
Intratracheal Injection

This study aimed to explore the effect of the TSLP–DC–OX40L pathway in asthma pathogenesis and airway inflammation in mice. For this, 65 male BALF/c mice were distributed among the control, asthma, immunoglobulin G (IgG) + asthma (IgG, 500 μg/500 μL, intratracheal injection of 50 μL each time), LY294002 (OX40L inhibitor) + asthma (intratracheal injection of 2 mg/kg LY294002), and anti-TSLP + asthma (intratracheal injection of 500 μg/500 μL TSLP antibody, 50 μL each time) groups. ELISA was applied to measure the serum levels of immunoglobulin E (IgE), ovalbumin (OVA)-sIgE, interleukin-4 (IL-4), IL-5, IL-13, and interferon-γ (IFN-γ); flow cytometry was employed to detect Treg cells and dendritic cell (DC) and lymphopoiesis. RT–qPCR and Western blot assays were used to measure the levels of TSLP, OX40L, T-bet, GATA-3, NF-κB, p38, and ERK. Treatment with LY294002 and anti-TSLP resulted in increases in the numbers of total cells, eosinophils, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid; total serum levels of IgE, OVA-sIgE, IL-4, IL-5, and IL-13; levels of DC cells; lymphopoiesis; and levels of TSLP, OX40L, GATA-3, NF-κB, p38, and ERK, whereas there were decreases in the levels of IFN-γ and CD4+CD25+Treg cells; CD4+Foxp3+Treg cells; and T-bet. The TSLP–DC–OX40L pathway may contribute to asthma pathogenesis and airway inflammation by modulating the levels of CD4+CD25+Treg cells and inflammatory cytokines.

Paeonol attenuates airway inflammation and hyperresponsiveness in a murine model of ovalbumin-induced asthma

2010 ◽  
Vol 88 (10) ◽  
pp. 1010-1016 ◽  
Author(s):  
Qiang Du ◽  
Gan-Zhu Feng ◽  
Li Shen ◽  
Jin Cui ◽  
Jian-Kang Cai
Keyword(s):  
Bronchoalveolar Lavage ◽  
Airway Inflammation ◽  
Bronchoalveolar Lavage Fluid ◽  
Immunoglobulin E ◽  
Therapeutic Potential ◽  
Lavage Fluid ◽  
Interleukin 4 ◽  
Moutan Cortex ◽  
Ifn Γ ◽  
Anti Inflammatory

Paeonol, the main active component isolated from Moutan Cortex, possesses extensive pharmacological activities such as anti-inflammatory, anti-allergic, and immunoregulatory effects. In the present study, we examined the effects of paeonol on airway inflammation and hyperresponsiveness in a mouse model of allergic asthma. BALB/c mice sensitized and challenged with ovalbumin were administered paeonol intragastrically at a dose of 100 mg/kg daily. Paeonol significantly suppressed ovalbumin-induced airway hyperresponsiveness to acetylcholine chloride. Paeonol administration significantly inhibited the total inflammatory cell and eosinophil count in bronchoalveolar lavage fluid. Treatment with paeonol significantly enhanced IFN-γ levels and decreased interleukin-4 and interleukin-13 levels in bronchoalveolar lavage fluid and total immunoglobulin E levels in serum. Histological examination of lung tissue demonstrated that paeonol significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. These data suggest that paeonol exhibits anti-inflammatory activity in allergic mice and may possess new therapeutic potential for the treatment of allergic bronchial asthma.

scholarly journals The Effect of Curcuma longa on Inflammatory Mediators and Immunological, Oxidant, and Antioxidant Biomarkers in Asthmatic Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Mohammad Hossein Boskabady ◽  
Fatemeh Amin ◽  
Farzaneh Shakeri
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Immunoglobulin E ◽  
Curcuma Longa ◽  
Lavage Fluid ◽  
Interleukin 4 ◽  
Control Group ◽  
Ifn Γ ◽  
Wbc Count ◽  
Asthma Group ◽  
Eosinophil Counts

The effects of Curcuma longa (C. longa) on total and differential WBC, inflammatory and immunologic mediators, and oxidant and antioxidant biomarkers in bronchoalveolar lavage fluid (BALF) of rats model of asthma were assessed. Animals were divided to 5 groups including control (C), asthma (sensitized to ovalbumin), and asthmatic groups treated with 0.75, 1.50, and 3.00 mg/ml C. longa (CL) and 1.25 μg/ml dexamethasone (D) (8 rats in each group). Total and differential WBC count, concentrations of phospholipase A2 (PLA2), total protein (TP), interferon-gamma (IFN-γ), interleukin-4 (IL-4), immunoglobulin E (IgE), NO2, NO3, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and thiol in BALF were assessed. Total and most differential WBC counts and BALF levels of PLA2, TP, IgE, IL-4, and oxidants in asthma group were higher but antioxidants and IFN-γ levels as well as IFN-γ/IL-4 ratio were lower than control group ( p  < 0.001 for all cases). Total WBC and levels of PLA2, IgE, NO2, and NO3 were significantly reduced following treatment with C. longa, compared to asthma group ( p  < 0.001 for all cases). In groups treated with dexamethasone and two higher concentrations of C. longa, neutrophil and eosinophil counts as well as TP, IL-4, and MDA levels were significantly decreased but IFN-γ, IFN-γ/IL-4 ratio, and antioxidants were increased (except IFN-γ/IL-4 ratio), compared to asthma group ( p  < 0.05 to p  < 0.001). Compared to dexamethasone, C. longa exerted more pronounced effects on lung inflammation, oxidative stress, and immune system in asthmatic rats.

scholarly journals Allergen-Specific Treg Cells Upregulated by Lung-Stage S. japonicum Infection Alleviates Allergic Airway Inflammation

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhidan Li ◽  
Wei Zhang ◽  
Fang Luo ◽  
Jian Li ◽  
Wenbin Yang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Protective Effect ◽  
Airway Inflammation ◽  
Lung Tissue ◽  
Immunoglobulin E ◽  
Allergic Airway Inflammation ◽  
Treg Cells ◽  
Protective Effects ◽  
Novel Therapy ◽  
Allergen Sensitization

Schistosoma japonicum infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist especially regarding the timing of the helminth infection and the underlying mechanisms. Most previous studies focused on understanding the preventive effect of S. japonicum infection on asthma (infection before allergen sensitization), whereas the protective effects of S. japonicum infection (allergen sensitization before infection) on asthma were rarely investigated. In this study, we investigated the protective effects of S. japonicum infection on AAI using a mouse model of OVA-induced asthma. To explore how the timing of S. japonicum infection influences its protective effect, the mice were percutaneously infected with cercaria of S. japonicum at either 1 day (infection at lung-stage during AAI) or 14 days before ovalbumin (OVA) challenge (infection at post–lung-stage during AAI). We found that lung-stage S. japonicum infection significantly ameliorated OVA-induced AAI, whereas post–lung-stage infection did not. Mechanistically, lung-stage S. japonicum infection significantly upregulated the frequency of regulatory T cells (Treg cells), especially OVA-specific Treg cells, in lung tissue, which negatively correlated with the level of OVA-specific immunoglobulin E (IgE). Depletion of Treg cells in vivo partially counteracted the protective effect of lung-stage S. japonicum infection on asthma. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage S. japonicum infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage S. japonicum infection could relieve OVA-induced asthma in a mouse model. The protective effect was mediated by the upregulated OVA-specific Treg cells, which suppressed IgE production. Our results may facilitate the discovery of a novel therapy for AAI.

scholarly journals Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes

Gut ◽  
1998 ◽  
Vol 42 (5) ◽  
pp. 643-649 ◽  
Author(s):  
M Carol ◽  
A Lambrechts ◽  
A Van Gossum ◽  
M Libin ◽  
M Goldman ◽  
...  
Keyword(s):  
Lamina Propria ◽  
Intestinal Mucosa ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Gastrointestinal Diseases ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

Background—Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses.Aims—To quantify interferon γ (IFN-γ) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation.Patients—Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa.Methods—Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-γ and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT).Results—The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-γ SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-γ and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in the basal state, and 0.1% secreted IL-4.Conclusions—Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.

Effect of Ninjin-Youei-To on Th1/Th2 Type Cytokine Production in Different Mouse Strains

2002 ◽  
Vol 30 (02n03) ◽  
pp. 215-223 ◽  
Author(s):  
Tsutomu Nakada ◽  
Kenji Watanabe ◽  
Guang-Bi Jin ◽  
Kazuo Toriizuka ◽  
Toshihiko Hanawa
Keyword(s):  
Oral Administration ◽  
Cytokine Production ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Mouse Strains ◽  
Enzyme Linked Immunosorbent Assay ◽  
Herbal Formula ◽  
Beneficial Effects ◽  
Ifn Γ ◽  
Th1 And Th2

Ninjin-Youei-To (NYT; Ren-Shen-Yang-Rong-Tang in Chinese) is a traditional herbal formula, which is widely used in Japan, Korea and China to modulate physiological immunity. The effects of oral administration of NYT on cytokine production from splenocytes were investigated in both C57BL/6 and BALB/c mice in which Th1 and Th2 were dominant, respectively. Splenocytes from C57BL/6 and BALB/c mice, which took NYT orally for four weeks, were cultured with anti-mouse CD3 mAb, and the supernatant was examined for cytokine production using enzyme-linked immunosorbent assay (ELISA). Administration of NYT to C57BL/6 mice, increased the production of interleukin-4 (IL-4) significantly, and slightly decreased interferon-γ (IFN-γ) production from splenocytes. In contrast, the same treatment significantly increased IFN-γ secretion from splenocytes of BALB/c mice. No remarkable changes of IL-12 production from splenocytes were observed in either strain of mice. These results suggest that oral administration of NYT ameliorates the excessive inclination of Th1 and Th2 type cytokine production, and NYT may provide a beneficial effects for the treatment of diseases caused by a skewed Th1-Th2 balance in the immune system.

scholarly journals Apigenin Attenuates Allergic Responses of Ovalbumin-Induced Allergic Rhinitis Through Modulation of Th1/Th2 Responses in Experimental Mice

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582090479 ◽  
Author(s):  
Feng Chen ◽  
Dongyun He ◽  
Bailing Yan
Keyword(s):  
Allergic Rhinitis ◽  
Messenger Rna ◽  
Immunoglobulin E ◽  
Elevated Serum ◽  
Lavage Fluid ◽  
Specific Ige ◽  
Cytokine Signaling ◽  
Nuclear Factor ◽  
Th2 Response ◽  
Ifn Γ

Background: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated immune-inflammatory response mainly affecting nasal mucosa. Apigenin, a flavonoid, has been documented to possess promising anti-allergic potential. Aim: To determine the potential mechanism of action of apigenin against ovalbumin (OVA)-induced AR by assessing various behavioral, biochemical, molecular, and ultrastructural modifications. Materials and Methods: Allergic rhinitis was induced in BALB/c mice (18-22 grams) by sensitizing it with OVA (5%, 500 μL, intraperitoneal [IP] on each consecutive day, for 13 days) followed by intranasal challenge with OVA (5%, 5 μL per nostril on day 21). Animals were treated with either vehicle (distilled water, 10 mg/kg, IP) or apigenin (5, 10, and 20 mg/kg, IP). Results: Intranasal challenge of OVA resulted in significant induction ( P < .05) of AR reflected by an increase in nasal symptoms (sneezing, rubbing, and discharge), which were ameliorated significantly ( P < .05) by apigenin (10 and 20 mg/kg) treatment. It also significantly inhibited ( P < .05) OVA-induced elevated serum histamine, OVA-specific IgE, total IgE, and IgG1 and β-hexosaminidase levels. Ovalbumin-induced increased levels of interleukin (IL)-4, IL-5, IL-13, and interferon (IFN)-γ in nasal lavage fluid were significantly decreased ( P < .05) by apigenin. Ovalbumin-induced alterations in splenic GATA binding protein 3 (ie, erythroid transcription factor) (GATA3), T-box protein expressed in T cells (T-bet), signal transducer and activator of transcription-6 (STAT6), suppressor of cytokine signaling 1 (SOCS1), nuclear factor-kappa B (NF-κB), and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha messenger RNA, as well as protein expressions were significantly inhibited ( P < .05) by apigenin. It also significantly ameliorated ( P < .05) nasal and spleen histopathologic and ultrastructure aberration induced by OVA. Conclusion: Apigenin regulates Th1/Th2 balance via suppression in expressions of Th2 response (IgE, histamine, ILs, GATA3, STAT6, SOCS1, and NF-κB) and activation of Th1 response (IFN-γ and T-bet) to exert its anti-allergic potential in a murine model of OVA-induced AR.

scholarly journals The Study of a Possible Correlation between Serum Levels of Interleukin 17 and Clinical Severity in Patients with Allergic Rhinitis

2017 ◽  
Vol 8 (3) ◽  
pp. ar.2017.8.0207
Author(s):  
Mai Aly Gharib Aly ◽  
Mohamed Tawfik El Tabbakh ◽  
Waheed Fawzy Heissam ◽  
Said Hamed Abbadi
Keyword(s):  
Allergic Rhinitis ◽  
Immunoglobulin E ◽  
Skin Testing ◽  
Allergic Diseases ◽  
Serum Levels ◽  
Clinical Severity ◽  
Total Serum ◽  
Interleukin 17 ◽  
Serum Ige ◽  
Cluster Immunotherapy

Introduction Allergic rhinitis (AR) is one of the most common allergic diseases, which affects ~20% of the world's population. T-helper (Th) type 2 cells produce interleukin (IL) 4 and IL-13, and mediate allergic responses, and these cytokines have been extensively studied as key players in the atopic airway diseases. However, the involvement of Th17 cells and IL-17 in AR has not been clearly examined. Aim To reevaluate AR clinical severity with serum IL-17, whether IL-17 affects the disease alone or in contribution with the atopic predisposition. Patients and Methods During an 18-month period, 39 individuals were divided into three groups: A, (13 control), B (13 with mild-to-moderate AR), and C (13 with severe AR). Both group B and group C patients (26) were subjected to clinical examination and allergy skin testing, and to measurement of both total serum immunoglobulin E (IgE) and IL-17 levels. Eleven patients with AR then were exposed to 6 months of cluster immunotherapy, whereas the rest of the patients were not exposed. Results Revealed a significant elevation of serum IL-17 levels with an associated increase in serum IgE in the patients with AR compared with controls and revealed that the serum levels of both total serum IgE and IL-17 decreased significantly after cluster immunotherapy. Conclusion These preliminary results added new data about the use of injective immunotherapy as well as reported on the use of sublingual immunotherapy.

scholarly journals Phloretin alleviates dinitrochlorobenzene-induced dermatitis in BALB/c mice

2020 ◽  
Vol 34 ◽  
pp. 205873842092944
Author(s):  
Chieh-Shan Wu ◽  
Shih-Chao Lin ◽  
Shiming Li ◽  
Yu-Chih Chiang ◽  
Nicole Bracci ◽  
...  
Keyword(s):  
Mouse Model ◽  
Serum Levels ◽  
Interferon Γ ◽  
Chronic Inflammatory Disease ◽  
Mitogen Activated Protein Kinase ◽  
Normal Ranges ◽  
Mitogen Activated Protein ◽  
Ifn Γ ◽  
Allergic Contact

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that substantially affects a patient’s quality of life. While steroids are the most common therapy used to temporally alleviate the symptoms of AD, effective and nontoxic alternatives are urgently needed. In this study, we utilized a natural, plant-derived phenolic compound, phloretin, to treat allergic contact dermatitis (ACD) on the dorsal skin of mice. In addition, the effectiveness of phloretin was evaluated using a mouse model of ACD triggered by 2,4-dinitrochlorobenzene (DNCB). In our experimental setting, phloretin was orally administered to BALB/c mice for 21 consecutive days, and then, the lesions were examined histologically. Our data revealed that phloretin reduced the process of epidermal thickening and decreased the infiltration of mast cells into the lesion regions, subsequently reducing the levels of histamine and the pro-inflammatory cytokines interleukin (IL)-6, IL-4, thymic stromal lymphopoietin (TSLP), interferon-γ (IFN-γ) and IL-17A in the serum. These changes were associated with lower serum levels after phloretin treatment. In addition, we observed that the mitogen-activated protein kinase (MAPK) and NF-κB pathways in the dermal tissues of the phloretin-treated rodents were suppressed compared to those in the AD-like skin regions. Furthermore, phloretin appeared to limit the overproliferation of splenocytes in response to DNCB stimulation, reducing the number of IFN-γ-, IL-4-, and IL-17A-producing CD4+ T cells in the spleen back to their normal ranges. Taken together, we discovered a new therapeutic role of phloretin using a mouse model of DNCB-induced ACD, as shown by the alleviated AD-like symptoms and the reversed immunopathological effects. Therefore, we believe that phloretin has the potential to be utilized as an alternative therapeutic agent for treating AD.

Effects of the Japanese herbal medicine ‘Inchinko-to’ (TJ-135) on concanavalin A-induced hepatitis in mice

2000 ◽  
Vol 99 (5) ◽  
pp. 421-431 ◽  
Author(s):  
Masayoshi YAMASHIKI ◽  
Akihito MASE ◽  
Ichiro ARAI ◽  
Xian-Xi HUANG ◽  
Tsutomu NOBORI ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Concanavalin A ◽  
Serum Levels ◽  
Interferon Γ ◽  
Hepatic Necrosis ◽  
Interleukin 12 ◽  
Con A ◽  
Ifn Γ

Inchinko-to (TJ-135) is a herbal medicine consisting of three kinds of crude drugs, and in Japan it is administered mainly to patients with cholestasis. The present study evaluated the effects of TJ-135 on concanavalin A (con A)-induced hepatitis in mice in vivo and con A-induced cytokine production in vitro. When mice were pretreated with oral TJ-135 for 1 week before intravenous con A injection, the activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were significantly decreased 8 h after con A administration (-82%, -96% and -66% respectively). In histological investigations, sub-massive hepatic necrosis accompanying inflammatory cell infiltration was not observed in mice pretreated with TJ-135. Serum levels of interleukin-12 (IL-12), interferon-γ (IFN-γ) and IL-2 were significantly lower in mice pretreated with TJ-135 compared with controls, while IL-10 levels were higher in these mice. Intrasplenic IL-12 levels were significantly lower in mice pretreated with TJ-135, while intrasplenic IL-10 levels were higher in these mice. In vitro, IL-10 production by splenocytes was increased by the addition of TJ-135 to the culture medium, whereas the production of IL-12 and IFN-γ was inhibited. These results suggest that con A-induced hepatitis was ameliorated by pretreatment with TJ-135. With regard to the mechanism of these effects of TJ-135, we speculate that TJ-135 inhibits the production of inflammatory cytokine and enhances the production of anti-inflammatory cytokines. Therefore administration of TJ-135 may be useful in patients with severe acute hepatitis accompanying cholestasis or in those with autoimmune hepatitis.

scholarly journals Effects of Respiratory Mycoplasma pneumoniae Infection on Allergen-Induced Bronchial Hyperresponsiveness and Lung Inflammation in Mice

2003 ◽  
Vol 71 (3) ◽  
pp. 1520-1526 ◽  
Author(s):  
Hong Wei Chu ◽  
Joyce M. Honour ◽  
Catherine A. Rawlinson ◽  
Ronald J. Harbeck ◽  
Richard J. Martin
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Lung Inflammation ◽  
Bronchial Hyperresponsiveness ◽  
Lavage Fluid ◽  
Interleukin 4 ◽  
Mycoplasma Infection ◽  
Temporary Reduction ◽  
Protein Levels ◽  
Asthma Model ◽  
Ifn Γ

ABSTRACT Airway mycoplasma infection may be associated with asthma pathophysiology. However, the direct effects of mycoplasma infection on asthma remain unknown. Using a murine allergic-asthma model, we evaluated the effects of different timing of airway Mycoplasma pneumoniae infection on bronchial hyperresponsiveness (BHR), lung inflammation, and the protein levels of Th1 (gamma interferon [IFN-γ]) and Th2 (interleukin 4 [IL-4]) cytokines in bronchoalveolar lavage fluid. When mycoplasma infection occurred 3 days before allergen (ovalbumin) sensitization and challenge, the infection reduced the BHR and inflammatory-cell influx into the lung. This was accompanied by a significant induction of Th1 responses (increased IFN-γ and decreased IL-4 production). Conversely, when mycoplasma infection occurred 2 days after allergen sensitization and challenge, the infection initially caused a temporary reduction of BHR and then increased BHR, lung inflammation, and IL-4 levels. Our data suggest that mycoplasma infection could modulate both physiological and immunological responses in the murine asthma model. Our animal models may also provide a new means to understand the role of infection in asthma pathogenesis and give evidence for the asthma hygiene hypothesis.

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