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Immunity, Inflammation and Disease Jun 2024Particulate β-glucans (WGP) are natural compounds with regulatory roles in various biological processes, including tumorigenesis and inflammatory diseases such as...
BACKGROUND
Particulate β-glucans (WGP) are natural compounds with regulatory roles in various biological processes, including tumorigenesis and inflammatory diseases such as allergic asthma. However, their impact on mast cells (MCs), contributors to airway hyperresponsiveness (AHR) and inflammation in asthma mice, remains unknown.
METHODS
C57BL/6 mice underwent repeated OVA sensitization without alum, followed by Ovalbumin (OVA) challenge. Mice received daily oral administration of WGP (OAW) at doses of 50 or 150 mg/kg before sensitization and challenge. We assessed airway function, lung histopathology, and pulmonary inflammatory cell composition in the airways, as well as proinflammatory cytokines and chemokines in the bronchoalveolar lavage fluid (BALF).
RESULTS
The 150 mg/kg OAW treatment mitigated OVA-induced AHR and airway inflammation, evidenced by reduced airway reactivity to aerosolized methacholine (Mch), diminished inflammatory cell infiltration, and goblet cell hyperplasia in lung tissues. Additionally, OAW hindered the recruitment of inflammatory cells, including MCs and eosinophils, in lung tissues and BALF. OAW treatment attenuated proinflammatory tumor necrosis factor (TNF)-α and IL-6 levels in BALF. Notably, OAW significantly downregulated the expression of chemokines CCL3, CCL5, CCL20, CCL22, CXCL9, and CXCL10 in BALF.
CONCLUSION
These results highlight OAW's robust anti-inflammatory properties, suggesting potential benefits in treating MC-dependent AHR and allergic inflammation by influencing inflammatory cell infiltration and regulating proinflammatory cytokines and chemokines in the airways.
Topics: Animals; Asthma; Mast Cells; Mice; Disease Models, Animal; Administration, Oral; Mice, Inbred C57BL; beta-Glucans; Cytokines; Inflammation; Ovalbumin; Respiratory Hypersensitivity; Bronchoalveolar Lavage Fluid; Lung
PubMed: 38934407
DOI: 10.1002/iid3.1333 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2024To explore the effects of iris xanthin on airway inflammation, airway remodeling, and the high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear...
OBJECTIVES
To explore the effects of iris xanthin on airway inflammation, airway remodeling, and the high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in asthmatic young mice.
METHODS
Sixty male BALB/c young mice were randomly assigned into six groups: a blank group, a model group, a dexamethasone group, and low, medium, and high dose groups of iris xanthin, with ten mice per group. Asthma models were induced through intraperitoneal injections of a sensitizing agent [ovalbumin (OVA) 20 μg + aluminum hydroxide gel 2 mg], followed by 4% OVA aerosol inhalation. Lung function was measured using a pulmonary function tester to determine lung volume (LV), resting ventilation per minute (VE), and airway reactivity (Penh value). Hematoxylin-eosin (HE) staining was employed to examine and analyze airway remodeling. The contents of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid were quantified using ELISA. Real-time fluorescence quantitative polymerase chain reaction and Western blot analysis were used to assess the expression of HMGB1/TLR4/NF-κB pathway-related mRNA and proteins in lung tissues.
RESULTS
Compared to the model group, the dexamethasone and iris xanthin-treated groups (low, medium, and high doses) exhibited significant increases in LV and VE (<0.05), with incremental dose-dependent increases observed in the iris xanthin groups. Additionally, Penh values, IL-1β, IL-6, TNF-α, and airway remodeling indicators, along with mRNA levels of HMGB1, TLR4, and NF-κB p65 and protein levels of HMGB1, TLR4, and p-NF-κB p65, were all reduced (<0.05) in a dose-dependent manner. When compared to the dexamethasone group, the low and medium dose iris xanthin groups showed decreases in LV and VE (<0.05), whereas Penh values, IL-1β, IL-6, TNF-α, and airway remodeling indicators, along with mRNA levels of HMGB1, TLR4, NF-κB p65 and protein levels of HMGB1, TLR4, and p-NF-κB p65, were increased (<0.05). No significant differences were noted in these indices between the high dose iris xanthin group and the dexamethasone group (>0.05).
CONCLUSIONS
Iris xanthin can effectively alleviates airway inflammation and inhibits airway remodeling in asthmatic young mice, possibly through the suppression of the HMGB1/TLR4/NF-κB pathway.
Topics: Animals; Airway Remodeling; Asthma; Male; Mice; Toll-Like Receptor 4; Mice, Inbred BALB C; HMGB1 Protein; NF-kappa B; Signal Transduction
PubMed: 38926382
DOI: 10.7499/j.issn.1008-8830.2312023 -
Frontiers in Immunology 2024Allergen-specific immunotherapy (AIT) is able to restore immune tolerance to allergens in allergic patients. However, some patients do not or only poorly respond to...
BACKGROUND
Allergen-specific immunotherapy (AIT) is able to restore immune tolerance to allergens in allergic patients. However, some patients do not or only poorly respond to current treatment protocols. Therefore, there is a need for deeper mechanistic insights and further improvement of treatment strategies. The relevance of the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, has been investigated in several inflammatory diseases, including allergic asthma. However, its potential role in AIT still needs to be addressed.
METHODS
A murine model of AIT in ovalbumin-induced allergic airway inflammation was performed in AhR-deficient (AhR) and wild-type mice. Furthermore, AIT was combined with the application of the high-affinity AhR agonist 10-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ) as an adjuvant to investigate the effects of AhR activation on therapeutic outcome.
RESULTS
Although AhR mice suffer stronger allergic responses than wild-type mice, experimental AIT is comparably effective in both. Nevertheless, combining AIT with the administration of 10-Cl-BBQ improved therapeutic effects by an AhR-dependent mechanism, resulting in decreased cell counts in the bronchoalveolar fluid, decreased pulmonary Th2 and Th17 cell levels, and lower sIgE levels.
CONCLUSION
This study demonstrates that the success of AIT is not dependent on the AhR. However, targeting the AhR during AIT can help to dampen inflammation and improve tolerogenic vaccination. Therefore, AhR ligands might represent promising candidates as immunomodulators to enhance the efficacy of AIT.
Topics: Animals; Receptors, Aryl Hydrocarbon; Mice; Desensitization, Immunologic; Allergens; Disease Models, Animal; Mice, Knockout; Asthma; Adjuvants, Immunologic; Ovalbumin; Female; Mice, Inbred C57BL; Th2 Cells; Basic Helix-Loop-Helix Transcription Factors
PubMed: 38915403
DOI: 10.3389/fimmu.2024.1397072 -
PloS One 2024The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This...
The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-β, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5'-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis.
Topics: Animals; Asthma; Rosuvastatin Calcium; AMP-Activated Protein Kinases; Signal Transduction; Airway Remodeling; Mice; Disease Models, Animal; Ovalbumin; Female; Mice, Inbred BALB C; Bronchoalveolar Lavage Fluid; Chronic Disease; Inflammation; Lung; Immunoglobulin E
PubMed: 38913666
DOI: 10.1371/journal.pone.0305863 -
International Journal of Molecular... Jun 2024The nanosized vesicles secreted from various cell types into the surrounding extracellular space are called extracellular vesicles (EVs). Although mesenchymal stem...
The nanosized vesicles secreted from various cell types into the surrounding extracellular space are called extracellular vesicles (EVs). Although mesenchymal stem cell-derived EVs are known to have immunomodulatory effects in asthmatic mice, the role of identified pulmonary genes in the suppression of allergic airway inflammation remains to be elucidated. Moreover, the major genes responsible for immune regulation in allergic airway diseases have not been well documented. This study aims to evaluate the immunomodulatory effects of secretoglobin family 1C member 1 (SCGB1C1) on asthmatic mouse models. C57BL/6 mice were sensitized to ovalbumin (OVA) using intraperitoneal injection and were intranasally challenged with OVA. To evaluate the effect of SCGB1C1 on allergic airway inflammation, 5 μg/50 μL of SCGB1C1 was administrated intranasally before an OVA challenge. We evaluated airway hyperresponsiveness (AHR), total inflammatory cells, eosinophils in the bronchoalveolar lavage fluid (BALF), lung histology, serum immunoglobulin (Ig), the cytokine profiles of BALF and lung-draining lymph nodes (LLN), and the T cell populations in LLNs. The intranasal administration of SCGB1C1 significantly inhibited AHR, the presence of eosinophils in BALF, eosinophilic inflammation, goblet cell hyperplasia in the lung, and serum total and allergen-specific IgE. SCGB1C1 treatment significantly decreased the expression of interleukin (IL)-5 in the BALF and IL-4 in the LLN, but significantly increased the expression of IL-10 and transforming growth factor (TGF)-β in the BALF. Furthermore, SCGB1C1 treatment notably increased the populations of CD4CD25Foxp3 regulatory T cells (Tregs) in asthmatic mice. The intranasal administration of SCGB1C1 provides a significant reduction in allergic airway inflammation and improvement of lung function through the induction of Treg expansion. Therefore, SCGB1C1 may be the major regulator responsible for suppressing allergic airway inflammation.
Topics: Animals; T-Lymphocytes, Regulatory; Mice; Asthma; Mice, Inbred C57BL; Ovalbumin; Lung; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Immunoglobulin E; Female; Inflammation; Eosinophils
PubMed: 38892470
DOI: 10.3390/ijms25116282 -
Polymers May 2024Sample pretreatment is a key step for qualitative and quantitative analysis of trace substances in complex samples. Cis-dihydroxyl (cis-diol) group-containing substances...
Sample pretreatment is a key step for qualitative and quantitative analysis of trace substances in complex samples. Cis-dihydroxyl (cis-diol) group-containing substances exist widely in biological samples and can be selectively bound by boronate affinity adsorbents. Based on this, in this article, we proposed a simple method for the preparation of novel spherical three-dimensionally ordered macropore (3DOM) materials based on a combination of the boronate affinity technique and colloidal crystal template method. The prepared 3DOM materials were characterized using Fourier transform-infrared spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, and thermo-gravimetric analysis, and results showed that they possessed the characteristics of a high specific surface area, high porosity, and more boronic acid recognition sites. The adsorption performance evaluation results showed that the maximum adsorption capacity of the boron affinity 3DOMs on ovalbumin (OVA) could reach to 438.79 mg/g. Kinetic and isothermal adsorption experiments indicated that the boronate affinity 3DOM material exhibited a high affinity and selectivity towards OVA and adenosine. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the proteins in egg whites was conducted and proved that the glycoprotein in the egg whites could be separated and enriched with a good performance. Therefore, a novel boronate affinity 3DOM material a with highly ordered and interconnected pore structure was prepared and could be applied in the separation and enrichment of molecules with cis-diol groups from complex samples with a good selectivity, efficiency, and high throughput.
PubMed: 38891485
DOI: 10.3390/polym16111539 -
Immunity, Inflammation and Disease Jun 2024For decades, studies have demonstrated the anti-inflammatory potential of proteins secreted by helminths in allergies and asthma. Previous studies have demonstrated the...
BACKGROUND
For decades, studies have demonstrated the anti-inflammatory potential of proteins secreted by helminths in allergies and asthma. Previous studies have demonstrated the immunomodulatory capabilities of Succinate Coenzyme A ligase beta-like protein (SUCLA-β) derived from Trichinella spiralis, a crucial excretory product of this parasite.
OBJECTIVE
To explore the therapeutic potential of SUCLA-β in alleviating and controlling ovalbumin (OVA)-induced allergic asthma, as well as its influence on host immune modulation.
METHODS
In this research, we utilized the rTs-SUCLA-β protein derived from T. spiralis to investigate its potential in mitigating airway inflammation in a murine model of asthma induced by OVA sensitization/stimulation, both pre- and post-challenge. The treatment's efficacy was assessed by quantifying the extent of inflammation in the lungs.
RESULTS
Treatment with rTs-SUCLA-β demonstrated efficacy in ameliorating OVA-induced airway inflammation, as evidenced by a reduction in eosinophil infiltration, levels of OVA-specific Immunoglobulin E, interferon-γ, interleukin (IL)-9, and IL-17A, along with an elevation in IL-10. The equilibrium between Th17 and Treg cells plays a pivotal role in modulating the abundance of inflammatory cells within the organism, thereby ameliorating inflammation and alleviating symptoms associated with allergic asthma.
CONCLUSIONS AND CLINICAL RELEVANCE
Our data revealed that T. spiralis-derived Ts-SUCLA-β protein may inhibit the allergic airway inflammation by regulating host immune responses.
Topics: Trichinella spiralis; Animals; Asthma; Mice; Ovalbumin; Helminth Proteins; Mice, Inbred BALB C; Disease Models, Animal; Female; Cytokines; Immunoglobulin E; Lung; T-Lymphocytes, Regulatory; Hypersensitivity; Th17 Cells
PubMed: 38888451
DOI: 10.1002/iid3.1321 -
Immunobiology Jul 2024Recent evidence has shown that T cell exhaustion is implicated in Allergen-specific Immunotherapy (AIT). However, how T cell exhaustion plays a role in AIT is far from...
Recent evidence has shown that T cell exhaustion is implicated in Allergen-specific Immunotherapy (AIT). However, how T cell exhaustion plays a role in AIT is far from clear. Our study aimed to investigate T cell exhaustion associated with allergen exposure during AIT in mice. Ovalbumin (OVA) - sensitized C57BL/6J asthma mouse and AIT mouse models were constructed. Quantitative real-time PCR (qRTPCR) and flow cytometry were used to monitor the occurrence of local and systemic CD4 T cells and Th2T cells exhaustion in OVA-sensitized mice. The inhibitory surface marker programmed cell death protein 1 (PD-1) on CD4 T cells and Th2T cells was significantly upregulated in AIT mice compared with asthmatic and control mice. The level of PD-1 on the surface of CD4T cells of asthma mice was significantly higher than that of control mice. The inhibitory surface marker cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on CD4 T cells and Th2T cells showed no significant difference between the AIT, asthma and control mice. Collectively, our study indicated that the expression of PD-1 on CD4 T cells and Th2T cells was increased in AIT. Allergen exposure promotes the expression of PD-1 on the surface of CD4 T cells. T cell exhaustion plays an important role in AIT.
Topics: Animals; Programmed Cell Death 1 Receptor; Mice; CD4-Positive T-Lymphocytes; Asthma; Allergens; Desensitization, Immunologic; Th2 Cells; Mice, Inbred C57BL; Disease Models, Animal; Female; Biomarkers; Ovalbumin
PubMed: 38875763
DOI: 10.1016/j.imbio.2024.152824 -
Chemical Science Jun 2024The amyloid states of proteins are implicated in several neurodegenerative diseases and bioadhesion processes. However, the classical amyloid fibrillization mechanism...
The amyloid states of proteins are implicated in several neurodegenerative diseases and bioadhesion processes. However, the classical amyloid fibrillization mechanism fails to adequately explain the formation of polymorphic aggregates and their adhesion to various surfaces. Herein, we report a non-fibril amyloid aggregation pathway, with disulfide-bond-reduced lysozyme (R-Lyz) as a model protein under quasi-physiological conditions. Very different from classical fibrillization, this pathway begins with the air-water interface (AWI) accelerated oligomerization of unfolded full-length protein, resulting in unique plate-like oligomers with self-adaptive ability, which can adjust their conformations to match various interfaces such as the asymmetric AWI and amyloid-protein film surface. The pathway enables a stepwise packing of the plate-like oligomers into a 2D Janus nanofilm, exhibiting a divergent distribution of hydrophilic/hydrophobic residues on opposite sides of the nanofilm. The resulting Janus nanofilm possesses a top-level Young's modulus (8.3 ± 0.6 GPa) among amyloid-based materials and exhibits adhesive strength two times higher (145 ± 81 kPa) than that of barnacle cement. Furthermore, we found that such an interface-directed pathway exists in several amyloidogenic proteins with a similar self-adaptive 2D-aggregation process, including bovine serum albumin, insulin, fibrinogen, hemoglobin, lactoferrin, and ovalbumin. Thus, our findings on the non-fibril self-adaptive mechanism for amyloid aggregation may shed light on polymorphic amyloid assembly and their adhesions through an alternative pathway.
PubMed: 38873054
DOI: 10.1039/d4sc00560k -
Journal For Immunotherapy of Cancer Jun 2024Adoptive cancer immunotherapy, using engineered T-cells, expressing chimeric antigen receptor or autologous tumor infiltrating lymphocytes became, in recent years, a...
BACKGROUND
Adoptive cancer immunotherapy, using engineered T-cells, expressing chimeric antigen receptor or autologous tumor infiltrating lymphocytes became, in recent years, a major therapeutic approach for diverse types of cancer. However, despite the transformative potential of adoptive cancer immunotherapy, this field still faces major challenges, manifested by the apparent decline of the cytotoxic capacity of effector CD8 T cells upon their expansion. To address these challenges, we have developed an ex vivo "synthetic immune niche" (SIN), composed of immobilized CCL21 and ICAM1, which synergistically induce an efficient expansion of antigen-specific CD8 T cells while retaining, and even enhancing their cytotoxic potency.
METHODS
To explore the molecular mechanisms through which a CCL21+ICAM1-based SIN modulates the interplay between the proliferation and cytotoxic potency of antigen-activated and CD3/CD28-activated effector CD8 T cells, we performed integrated analysis of specific differentiation markers via flow cytometry, together with gene expression profiling.
RESULTS
On day 3, the transcriptomic effect induced by the SIN was largely similar for both dendritic cell (DC)/ovalbumin (OVA)-activated and anti-CD3/CD28-activated cells. Cell proliferation increased and the cells exhibited high killing capacity. On day 4 and on, the proliferation/cytotoxicity phenotypes became radically "activation-specific"; The DC/OVA-activated cells lost their cytotoxic activity, which, in turn, was rescued by the SIN treatment. On longer incubation, the cytotoxic activity further declined, and on day7, could not be rescued by the SIN. SIN stimulation following activation with anti-CD3/CD28 beads induced a major increase in the proliferative phenotype while transiently suppressing their cytotoxicity for 2-3 days and fully regaining their killing activity on day 7. Potential molecular regulatory pathways of the SIN effects were identified, based on transcriptomic and multispectral imaging profiling.
CONCLUSIONS
These data indicate that cell proliferation and cytotoxicity are negatively correlated, and the interplay between them is differentially regulated by the mode of initial activation. The SIN stimulation greatly enhances the cell expansion, following both activation modes, while displaying high survival and cytotoxic potency at specific time points following stimulation, suggesting that it could effectively reinforce adoptive cancer immunotherapy.
Topics: Cell Proliferation; Humans; Intercellular Adhesion Molecule-1; Chemokine CCL21; Lymphocyte Activation; Immunotherapy, Adoptive; CD8-Positive T-Lymphocytes; Cytotoxicity, Immunologic
PubMed: 38866588
DOI: 10.1136/jitc-2024-009011