Amelioration of ovalbumin induced allergic symptoms in Balb/c mice by potentially probiotic strains of lactobacilli

2015 ◽  
Vol 6 (5) ◽  
pp. 669-678 ◽  
Author(s):  
M. Nawaz ◽  
C. Ma ◽  
M.A.R Basra ◽  
J. Wang ◽  
J. Xu

To evaluate the antiallergic effect of newly characterised probiotic strains, Lactobacillus fermentum NWS29, Lactobacillus casei NWP08 and Lactobacillus rhamnosus NWP13, mice were divided into six experimental groups: control, ovalbumin (OVA), NWS29, NWP08, NWP13 and L. rhamnosus GG (LGG). Mice were immunised and probiotics were administered via oral gavage followed by challenge with OVA. After last challenge with OVA, inflammatory cells in bronchoalveolar lavage fluid (BALF), recruitment of inflammatory cells in airways and OVA-specific immunoglobulin E (IgE) in serum were determined by Giemsa, haematoxylin and eosin (HE) staining, and ELISA, respectively. Relative mRNA expression of interleukins (IL-4, IL-5, IL-10, IL-13 and IL-17), transforming growth factor-β (TGF-β) and interferon-γ (IFN-γ) in lung and spleen tissue was determined by real time RT-PCR. OVA-specific IgE levels, recruitment of eosinophils and mRNA expressions of inflammatory cytokines were remarkably increased in OVA-exposed mice compared with the control group. Administration of NWS29 and NWP13 suppressed inflammatory cell infiltration in airways and BALF, and level of OVA-specific IgE in serum of OVA-exposed mice. Furthermore, NWS29 and NWP13 also abrogated the mRNA expression of 1L-4, IL-5, IL-13 and TGF-β in mice immunised and exposed to OVA. Our findings suggest that NWS29 and NWP13 might be good candidates for the prevention of allergic airway inflammation.

2007 ◽  
Vol 14 (3) ◽  
pp. 211-219 ◽  
Author(s):  
Rob J. Vandebriel ◽  
Eric R. Gremmer ◽  
Michiel van Hartskamp ◽  
Jan A. M. A. Dormans ◽  
Frits R. Mooi

ABSTRACT We have previously shown that in mice, diphtheria-tetanus-acellular pertussis (DTaP) vaccination before Bordetella pertussis infection resulted in, besides effective clearance, immediate hypersensitivity (lung eosinophilia, increased total serum immunoglobulin E [IgE], and increased ex vivo Th2 cytokine production by cells from the bronchial lymph nodes). To better appreciate the extent of these findings, we measured DTaP vaccination effects in the local lymph node assay (LLNA) and an ovalbumin (OVA) lung allergy model. In the LLNA, mice were vaccinated or adjuvant treated before being sensitized with trimellitic anhydride (TMA; inducing a Th2-directed response) and dinitrochlorobenzene (DNCB; inducing a Th1-directed response). Compared to the adjuvant-treated controls, the vaccinated mice showed a decreased response to TMA and (to a much lesser extent) an increased response to DNCB. The decreased response to TMA coincided with increased transforming growth factor β levels. With the exception of filamentous hemagglutinin, all vaccine constituents contributed to the decreased response to TMA. In the lung allergy model, sensitization induced OVA-specific IgE, lung pathology (peribronchiolitis, perivasculitis, and hypertrophy of the bronchiolar mucus cells) and increased the number of eosinophils, lymphocytes, and neutrophils in the bronchoalveolar lavage fluid. Vaccination failed to modulate these parameters. In conclusion, although DTaP vaccination may affect the LLNA response, we found no evidence of an effect on lung allergy.


2009 ◽  
Vol 297 (3) ◽  
pp. L411-L419 ◽  
Author(s):  
Ulaganathan Mabalirajan ◽  
Jyotirmoi Aich ◽  
Anurag Agrawal ◽  
Balaram Ghosh

Asthma is a dynamic disorder of airway inflammation and airway remodeling with an imbalance in T helper type 1 (Th1)/Th2 immune response. Increased Th2 cytokines such as IL-4 and IL-13 induce arginase either directly or indirectly through transforming growth factor-β1 (TGF-β1) and lead to subepithelial fibrosis, which is a crucial component of airway remodeling. Synthetic antimalarials have been reported to have immunomodulatory properties. Mepacrine is known for its reduction of airway inflammation in short-term allergen challenge model by reducing Th2 cytokines and cysteinyl leukotrienes, which has an important role in the development of airway remodeling features. Therefore, we hypothesized that mepacrine may reduce airway remodeling. For this, extended subacute ovalbumin mice model of asthma was developed; these mice showed an increased expression of profibrotic mediators, subepithelial fibrosis, and goblet cell metaplasia along with airway inflammation, increased Th2 cytokines, allergen-specific IgE, IgG1, increased cytosolic PLA2 (cPLA2), and airway hyperresponsiveness. Presence of intraepithelial eosinophils and significant TGF-β1 expression in subepithelial mesenchymal regions by repeated allergen exposures indicate that asthmatic mice of this study have developed human mimicking as well as late stages of asthma. However, mepacrine treatment decreased Th2 cytokines and subepithelial fibrosis and alleviated asthma features. These reductions by mepacrine were associated with a decrease in levels and expression of TGF-β1 and the reduction in activity, expression of arginase in lung cytosol, and immunolocalization in inflammatory cells present in perivascular and peribronchial regions. These results suggest that mepacrine might reduce the development of subepithelial fibrosis by reducing the arginase and TGF-β1. These effects of mepacrine likely underlie its antiairway remodeling action in asthma.


Author(s):  
Hui-Hsien Pan ◽  
Jiunn-Liang Ko ◽  
Chia-Ta Wu ◽  
Hai-Lun Sun ◽  
Yeak-Wun Quek ◽  
...  

<b><i>Background:</i></b> Asthma animal models provide valuable information about the pathogenesis and the treatment of asthma. An ovalbumin (OVA)/complete Freund’s adjuvant (CFA)-sensitized model was developed to induce neutrophil-dominant asthma and to investigate whether fungal immunomodulatory peptide-<i>fve</i> (FIP-<i>fve</i>) could improve asthma features in the OVA/CFA-sensitized model. <b><i>Methods:</i></b> We used female BALB/c mice and sensitized them intraperitoneally with OVA/CFA on days 1, 2, and 3. On days 14, 17, 21, 24, and 27, they were challenged with intranasal OVA. The airway hyper-responsiveness (AHR) was detected by BUXCO, inflammatory cells were stained with Liu’s stain, the cytokines were detected using ELISA, and the airway inflammation was analyzed with hematoxylin and eosin stain. <b><i>Results:</i></b> According to the results, OVA/CFA sensitization could induce AHR, high levels of IgE, and inflammatory cells especially neutrophils infiltration in the lung and airway inflammation. IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17, IL-25, IL-33, and transforming growth factor-β (TGF-β) increased in the OVA/CFA-sensitized mice. OVA/CFA-sensitized mice treated with FIP-<i>fve</i> not only increased IL-12 and IFN-γ but also decreased IL-4, IL-5, IL-6, IL-8, IL-13, IL-17, IL-25, IL-33, and TGF-β in the bronchoalveolar lavage fluid. Moreover, FIP-<i>fve</i> significantly decreased neutrophil infiltration in the lung. <b><i>Conclusion:</i></b> The OVA/CFA model induced neutrophilic asthma successfully, and FIP-<i>fve</i> improved neutrophil-dominant asthma.


2020 ◽  
Vol 21 (20) ◽  
pp. 7761
Author(s):  
Roberta Fusco ◽  
Rosalba Siracusa ◽  
Ramona D’Amico ◽  
Marika Cordaro ◽  
Tiziana Genovese ◽  
...  

Pulmonary fibrosis is a progressive disease characterized by lung remodeling due to excessive deposition of extracellular matrix. In this study, the bleomycin experimental model of pulmonary fibrosis was employed to investigate the anti-fibrotic and immunomodulatory activity of the inhibition of MALT1 protease activity. Mice received a single intra-tracheal administration of bleomycin (1 mg/kg) in the presence or absence of MI-2, a selective MALT1 inhibitor, (a dose of 30 mg/kg administered intra-peritoneally 1 h after bleomycin and daily until the end of the experiment). Seven days after bleomycin instillation mice were sacrificed and bronchoalveolar lavage fluid analysis, measurement of collagen content in the lung, histology, molecular analysis and immunohistochemistry were performed. To evaluate mortality and body weight gain a subset of mice was administered daily with MI-2 for 21 days. Mice that received MI-2 showed decreased weight loss and mortality, inflammatory cells infiltration, cytokines overexpression and tissue injury. Moreover, biochemical and immunohistochemical analysis displayed that MI-2 was able to modulate the excessive production of reactive oxygen species and the inflammatory mediator upregulation induced by bleomycin instillation. Additionally, MI-2 demonstrated anti-fibrotic activity by reducing transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA) and receptor associated factor 6 (TRAF6) expression. The underlying mechanisms for the protective effect of MI-2 bleomycin induced pulmonary fibrosis may be attributed to its inhibition on NF-κB pathway. This is the first report showing the therapeutic role of MALT1 inhibition in a bleomycin model of pulmonary fibrosis, thus supporting further preclinical and clinical studies.


2019 ◽  
Vol 317 (1) ◽  
pp. L29-L38 ◽  
Author(s):  
Jie Yu ◽  
Kebin Li ◽  
Jie Xu

We hypothesized that indoor PM2.5 exposure from coal combustion exaggerates airway inflammation in the lung tissue of asthmatic mice induced with ovalbumin (OVA). Forty BALB/c mice, randomly divided into four groups ( n = 10 per group), were intratracheally instilled with normal saline alone, PM2.5 (2.5 mg/ml PM2.5 alone), OVA (15 μg/ml OVA alone), and PM2.5+OVA (2.5 mg/ml PM2.5 and 15 μg/ml OVA), respectively, four times at 2-wk intervals. Daily mean concentration of PM2.5 from indoor coal combustion was 156.95 μg/m3. The highest metal composition in PM2.5 was Zn (34.81 ± 1.8 μg/m3). Exposure to PM2.5+OVA significantly elevated IL-4 and decreased IFN-γ production in mice compared with the control ( P < 0.05). Exposure to PM2.5+OVA showed a significant increase in the protein levels of granulocyte-macrophage colony-stimulating factor and IL-8 and a decrease in the protein level of transforming growth factor-β1 in bronchoalveolar lavage fluid of mice compared with the control ( P < 0.05). The expression of IL-4 mRNA was significantly increased, whereas the expression of IFN-γ mRNA was decreased in lung tissue of the PM2.5+OVA group ( P < 0.05). The expression level of Foxp3 mRNA in the PM2.5+OVA group was significantly lower than that in the control group in lung tissue ( P < 0.05). Treatment with PM2.5+OVA promoted a prominent neutrophil sequestration into the lung parenchyma, goblet cell proliferation, and severe inflammatory cell infiltration in the airways. Exposure to PM2.5 from indoor coal combustion might induce airway inflammatory immune responses and exacerbate peribronchiolar inflammation due to infiltration of inflammatory cells into the airway submucosa and airway structural pathological changes.


2004 ◽  
Vol 72 (7) ◽  
pp. 4023-4030 ◽  
Author(s):  
Colin M. Fitzsimmons ◽  
Sarah Joseph ◽  
Frances M. Jones ◽  
Claus M. Reimert ◽  
Karl F. Hoffmann ◽  
...  

ABSTRACT Chemotherapy for blood-dwelling schistosomes kills the worms and exposes parasite antigen to the circulation. In many people from areas of endemicity, this treatment increases parasite-specific immunoglobulin E (IgE) and other Th2 responses in the months following therapy, responses that have been associated with subsequent resistance to reinfection. Here we investigate much earlier changes in immune reactions after praziquantel therapy in Schistosoma mansoni-infected fishermen working in an area of high transmission in Uganda. The subjects gave blood before treatment and at 1 and 21 days posttreatment. Blood cultures were incubated with schistosome soluble worm antigen (SWA) or soluble egg antigen (SEA). Interleukin-4 (IL-4), IL-5, IL-10, IL-13, gamma interferon, and transforming growth factor β levels were measured in the cultures and in plasma. A marked transient increase in plasma IL-5 levels was observed in 75% of the subjects (n = 48) by 1 day posttreatment. This response was dependent on pretreatment intensity of infection and was accompanied by a transient decrease in eosinophil numbers. One day posttreatment, blood cultures from the 16 subjects with the greatest increase in plasma IL-5 level (>100 pg/ml) displayed reduced IL-5, IL-13, and IL-10 responses to SWA, and in contrast to the rest of the cohort, these high-IL-5 subjects displayed reduced levels of SWA-specific IgE in plasma 21 days posttreatment. Twenty months after treatment, the intensity of reinfection was positively correlated with the increase in plasma IL-5 level seen 1 day posttreatment. These studies describe the heterogeneity in early immune reactions to treatment, identifying subgroups who have different patterns of reaction and who may have different capacities to mount the responses that have been associated with resistance to reinfection.


Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 1202-1212
Author(s):  
Aichun Zhang ◽  
Yangzi Jin

AbstractAllergic rhinitis (AR) is one of the most common chronic diseases. This study examined whether microRNA (miR)-182-5p plays a role in AR by regulating toll-like receptor 4 (TLR4). First, data demonstrated that TLR4 was a target of miR-182-5p. Subsequently, AR mouse model was established to explore the role of miR-182-5p and TLR4 in AR in vivo. Initially, quantitative reverse transcription-PCR (qRT-PCR) analysis indicated that miR-182-5p was downregulated, while TLR4 expression was upregulated in AR mice. Then we found that miR-182-5p mimic reduced the frequency of sneezing and nose rubbing of the AR mice. In addition, miR-182-5p mimic significantly increased ovalbumin (OVA)-specific IgE and leukotriene C4 expression levels in nasal lavage fluid (NLF) and serum of AR mice. miR-182-5p mimic decreased the number of inflammatory cells in NLF of AR mice. It also reduced the levels of inflammatory factors in the serum of AR mice, such as interleukin (IL)-4, IL-5, IL-13, IL-17 and tumor necrosis factor (TNF)-α, while increasing the release of IFN-γ and IL-2. Finally, miR-182-5p mimic inhibited NF-κB signaling pathway activation in AR mice. However, all effects of miR-182-5p mimic on AR mice were reversed by TLR4-plasmid. In conclusion, miR-182-5p/TLR4 axis may represent a novel therapeutic target for AR.


Author(s):  
Theresia Indah Budhy ◽  
Ira Arundina ◽  
Meircurius Dwi Condro Surboyo ◽  
Anisa Nur Halimah

Abstract Objectives The purpose of this study is to analyze the effects of rice husk liquid smoke in Porphyromonas gingivalis-induced periodontitis in the inflammatory and proliferation marker such as nuclear factor kappa β (NF-kB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), fibroblast growth factor 2 (FGF2), collagen type 1 (COL-1) expression, and the number of macrophages, lymphocytes, and fibroblasts. Materials and Methods Rice husk liquid smoke is obtained by the pyrolysis process. Porphyromonas gingivalis-induced periodontitis in 20 μL phosphate-buffered saline containing 1 × 109 CFU was injected into the lower anterior gingival sulcus of Wistar rats. The periodontitis was then treated with 20 μL/20 g body weight of rice husk liquid smoke once a day for 2 and 7 days, respectively. After treatment, the bone and lower anterior gingival sulcus were analyzed with immunohistochemistry and hematoxylin–eosin staining. Results The treatment of periodontitis with rice husk liquid smoke showed a lower NF-kB, TNF-α, and IL-6 expression and a higher TGF-β, FGF2, and COL-1 expression than the control after treatment for 2 and 7 days (p < 0.05), respectively. The number of macrophages and fibroblasts was also higher when compared with the control group (p < 0.05), but the number of lymphocytes was lower than the control (p < 0.05). Conclusion Rice husk liquid smoke showed its effects on Porphyromonas gingivalis-induced periodontitis with a decrease in inflammatory markers and an increase in proliferation markers. The development of a rice husk liquid smoke periodontitis treatment is promising.


2017 ◽  
Vol 181 (5) ◽  
pp. 118-118 ◽  
Author(s):  
I. Wagner ◽  
K. J. Geh ◽  
M. Hubert ◽  
G. Winter ◽  
K. Weber ◽  
...  

Cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN) are a promising new immunotherapeutic treatment option for canine atopic dermatitis (AD). The aim of this uncontrolled pilot study was to evaluate clinical and immunological effects of gelatine nanoparticle (GNP)-bound CpG ODN (CpG GNP) on atopic dogs. Eighteen dogs with AD were treated for 8 weeks (group 1, n=8) or 18 weeks (group 2, n=10). Before inclusion and after 2 weeks, 4 weeks, 6 weeks (group 1+2), 8 weeks, 12 weeks and 16 weeks (group 2) 75 µg CpG ODN/dog (bound to 1.5 mg GNP) were injected subcutaneously. Pruritus was evaluated daily by the owner. Lesions were evaluated and serum concentrations and mRNA expressions of interferon-γ, tumour necrosis factor-α, transforming growth factor-β, interleukin (IL) 10 and IL-4 (only mRNA expression) were determined at inclusion and after 8 weeks (group 1+2) and 18 weeks (group 2). Lesions and pruritus improved significantly from baseline to week 8. Mean improvements from baseline to week 18 were 23 per cent and 44 per cent for lesions and pruritus, respectively, an improvement of ≥50 per cent was seen in six out of nine and three out of six dogs, respectively. IL-4 mRNA expression decreased significantly. The results of this study show a clinical improvement of canine AD with CpG GNP comparable to allergen immunotherapy. Controlled studies are needed to confirm these findings.


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