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Nano Letters Nov 2023Intranasal vaccines can induce protective immune responses at the mucosa surface entrance, preventing the invasion of respiratory pathogens. However, the nasal barrier...
Intranasal vaccines can induce protective immune responses at the mucosa surface entrance, preventing the invasion of respiratory pathogens. However, the nasal barrier remains a major challenge in the development of intranasal vaccines. Herein, a transmucosal nanovaccine based on cationic fluorocarbon modified chitosan (FCS) is developed to induce mucosal immunity. In our system, FCS can self-assemble with the model antigen ovalbumin and TLR9 agonist CpG, effectively promoting the maturation and cross-presentation of dendritic cells. More importantly, it can enhance the production of secretory immunoglobin A (sIgA) at mucosal surfaces for those intranasally vaccinated mice, which in the meantime showed effective production of immunoglobulin G (IgG) systemically. As a proof-of-concept study, such a mucosal vaccine inhibits ovalbumin-expressing B16-OVA melanoma, especially its lung metastases. Our work presents a unique intranasal delivery system to deliver antigen across mucosal epithelia and promote mucosal and systemic immunity.
Topics: Mice; Animals; Ovalbumin; Immunity, Mucosal; Adjuvants, Immunologic; Antigens; Mucous Membrane; Vaccines; Mice, Inbred BALB C
PubMed: 37943583
DOI: 10.1021/acs.nanolett.3c03419 -
International Journal of Biological... Jun 2023The polymeric materials formed by proteins and polysaccharides through molecular interactions have attracted public attention. In this study, a novel binary complex...
The polymeric materials formed by proteins and polysaccharides through molecular interactions have attracted public attention. In this study, a novel binary complex consisting of ovalbumin (OVA) and fucoidan (FUC) was obtained by electrostatic self-assembly. The self-assembly properties and the formation mechanism of the OVA-FUC binary complex were investigated by changing the charging degree and density of complex through altering pH value and polysaccharides proportion. Structural changes during the OVA-FUC electrostatic self-assembly process were investigated by a phase diagram, ζ-potential, and particle size. The optimal conditions for preparing soluble OVA-FUC binary complex were determined by the protein retention rate and insoluble solids content. Results showed that the soluble OVA-FUC binary complex could be obtained at the pH of 3.5 to 5, and the insoluble OVA-FUC binary complex was generated at the pH of 2.5 to 3.5. The OVA-FUC binary complex (19 ± 0.29 mN/m) possessed a medium ability to reduce interfacial tension of the water-oil interface compared with OVA (15 ± 1.13 mN/m) and FUC (24 ± 0.3 mN/m), indicating that OVA-FUC binary complex has good amphiphilicity and can be applied as a potential pH-controlled emulsifier in function food systems for delivering bioactive substances.
Topics: Ovalbumin; Polysaccharides; Emulsifying Agents
PubMed: 37121411
DOI: 10.1016/j.ijbiomac.2023.124644 -
Journal of Ethnopharmacology Mar 2024Xiaoqinglong decoction (XQLD), first recorded in Shang Han Lun, is a traditional Chinese medicine prescribed for the treatment of allergic rhinitis (AR). XQLD alleviates...
ETHNOPHARMACOLOGICAL RELEVANCE
Xiaoqinglong decoction (XQLD), first recorded in Shang Han Lun, is a traditional Chinese medicine prescribed for the treatment of allergic rhinitis (AR). XQLD alleviates the clinical symptoms of AR by inhibiting the occurrence of an inflammatory response, but the specific regulatory mechanism remains unclear.
AIM OF THE STUDY
NLRP3-mediated pyroptosis is closely related to AR pathogenesis. Hence, this study aimed to explore the potential role of NLRP3-mediated pyroptosis pathway in the AR-associated pharmacological mechanism of XQLD.
MATERIALS AND METHODS
BALB/C mice models of AR was established by using ovalbumin (OVA) and aluminum hydroxide sensitization. After intragastric administration of different dosages of XQLD, nasal allergic symptoms were observed. The expression of OVA-sIgE and Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum was detected by ELISA. The histopathological morphology and expression of inflammatory factors in nasal mucosa along with pyroptosis were investigated. Molecular docking was performed to analyze the binding of representative compounds of XQLD with NLRP3. Activation of the NLRP3 inflammasome was detected by immunofluorescence and western blotting.
RESULTS
XQLD significantly improved the nasal allergic symptoms of mice, reduced the degree of goblet cell proliferation, mast cell infiltration, and collagen fiber hyperplasia in nasal mucosa. Meanwhile, it could downregulate the expression of Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum and nasal mucosa. XQLD significantly reduced the number of GSDMD and TUNEL double-positive cells and IL-1β and IL-18 expression. Molecular docking confirmed that seven representative compounds of XQLD had good binding properties with NLRP3 and were able to inhibit the activation of the NLRP3 inflammasome.
CONCLUSIONS
The representative compounds of XQLD might inhibit pyroptosis in nasal mucosa mediated by the NLRP3 inflammasome to helping the recovery of AR, which provides a new modern pharmacological proof for XQLD to treat AR.
Topics: Mice; Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; Interleukin-13; Mice, Inbred BALB C; Pyroptosis; Interleukin-4; Interleukin-5; Molecular Docking Simulation; Rhinitis, Allergic; Disease Models, Animal; Ovalbumin
PubMed: 38030025
DOI: 10.1016/j.jep.2023.117490 -
Immunopharmacology and Immunotoxicology Dec 2023Luteolin (LO) has been reported to be a potential drug for allergic rhinitis (AR). This paper explored the mechanism of LO in AR.
OBJECTIVE
Luteolin (LO) has been reported to be a potential drug for allergic rhinitis (AR). This paper explored the mechanism of LO in AR.
MATERIALS AND METHODS
Mice were treated with ovalbumin (OVA) to construct an AR model before LO or 3-methyladenine (3-MA) treatment. The frequency of nasal sneezing was counted. The nasal mucosa thickness was assessed by hematoxylin-eosin staining assay. The levels of anti-OVA-immunoglobulin E (IgE)/IgG2a, autophagy-related factors (Beclin1, LC3II/LC3I), and T helper cell 17 (Th17)/regulatory T cell (Treg) markers (interleukin (IL)-17A, retinoic acid receptor-related orphan nuclear receptor γt (RORγt)/IL-10, forkhead box P3 (Foxp3)) were detected through enzyme-linked immunosorbent assay, western blot, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Flow cytometry assay was performed to test the percentage of Th17 and Treg cells.
RESULTS
The nasal sneezing frequency, nasal mucosa thickness, and levels of anti-OVA-IgE, Beclin1, LC3II/LC3I, IL-17A as well as RORγt were enhanced whereas anti-OVA-IgG2a, IL-10, and Foxp3 levels were inhibited in a mouse model of OVA-induced AR, which were reversed by LO or 3-MA treatment.
CONCLUSIONS
LO restored Treg/Th17 balance to ameliorate AR in a mouse model.
Topics: Mice; Animals; Interleukin-10; Luteolin; T-Lymphocytes, Regulatory; Nuclear Receptor Subfamily 1, Group F, Member 3; Beclin-1; Sneezing; Rhinitis, Allergic; Ovalbumin; Th17 Cells; Immunoglobulin E; Immunoglobulin G; Forkhead Transcription Factors; Disease Models, Animal; Mice, Inbred BALB C
PubMed: 36946145
DOI: 10.1080/08923973.2023.2166527 -
The Journal of Clinical Investigation Nov 2023CD8+ T cells outnumber CD4+ cells in multiple sclerosis (MS) lesions associated with disease progression, but the pathogenic role and antigenic targets of these clonally...
CD8+ T cells outnumber CD4+ cells in multiple sclerosis (MS) lesions associated with disease progression, but the pathogenic role and antigenic targets of these clonally expanded effectors are unknown. Based on evidence that demyelination is necessary but not sufficient for disease progression in MS, we previously hypothesized that CNS-infiltrating CD8+ T cells specific for neuronal antigens directly drive the axonal and neuronal injury that leads to cumulative neurologic disability in patients with MS. We now show that demyelination induced expression of MHC class I on neurons and axons and resulted in presentation of a neuron-specific neoantigen (synapsin promoter-driven chicken ovalbumin) to antigen-specific CD8+ T cells (anti-ovalbumin OT-I TCR-transgenic T cells). These neuroantigen-specific effectors surveilled the CNS in the absence of demyelination but were not retained. However, upon induction of demyelination via cuprizone intoxication, neuroantigen-specific CD8+ T cells proliferated, accumulated in the CNS, and damaged neoantigen-expressing neurons and axons. We further report elevated neuronal expression of MHC class I and β2-microglobulin transcripts and protein in gray matter and white matter tracts in tissue from patients with MS. These findings support a pathogenic role for autoreactive anti-axonal and anti-neuronal CD8+ T cells in MS progression.
Topics: Humans; Multiple Sclerosis; CD8-Positive T-Lymphocytes; Axons; Neurons; Disease Progression
PubMed: 37676734
DOI: 10.1172/JCI162788 -
Pharmaceutical Biology Dec 2023Stigmasterol has significant anti-arthritis and anti-inflammatory effects, but its role in immune and inflammatory diseases is still unclear.
CONTEXT
Stigmasterol has significant anti-arthritis and anti-inflammatory effects, but its role in immune and inflammatory diseases is still unclear.
OBJECTIVE
The potential advantages of stigmasterol in asthma were explored in IL-13-induced BEAS-2B cells and asthmatic mice.
MATERIALS AND METHODS
The optimal target of stigmasterol was confirmed in asthma. After detecting the cytotoxicity of stigmasterol in BEAS-2B cells, 10 μg/mL and 20 μg/mL stigmasterol were incubated with the BEAS-2B cell model for 48 h, and anti-inflammation and antioxidative stress were verified. Asthmatic mice were induced by OVA and received 100 mg/kg stigmasterol for 7 consecutive days. After 28 days, lung tissues and BAL fluid were collected for the following study. To further verify the role of NK1-R, 0.1 μM WIN62577 (NK1-R specific antagonist), and 1 μM recombinant human NK1-R protein were applied.
RESULTS
NK1-R was the potential target of stigmasterol. When the concentration of stigmasterol is 20 μg/mL, the survival rate of BEAS-2B cells is about 98.4%, which is non-toxic. Stigmasterol exerted anti-inflammation and antioxidant stress in a dose-dependent manner and decreased NK1-R expression in IL-13-induced BEAS-2B. Meanwhile, assay also indicated the anti-inflammation and antioxidant stress of stigmasterol after OVA challenge. Stigmasterol inhibited inflammation infiltration and mucus hypersecretion, and NK1-R expression.
DISCUSSION AND CONCLUSIONS
The protective effect of stigmaterol on asthma and its underlying mechanism have been discussed in depth, providing a theoretical basis and more possibilities for its treatment of asthma.
Topics: Animals; Humans; Mice; Anti-Inflammatory Agents; Antioxidants; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Inflammation; Interleukin-13; Lung; Mice, Inbred BALB C; Ovalbumin; Receptors, Neurokinin-1; Respiratory Hypersensitivity; Stigmasterol
PubMed: 36788676
DOI: 10.1080/13880209.2023.2173252 -
Redox Biology May 2024Th2-high asthma is characterized by elevated levels of type 2 cytokines, such as interleukin 13 (IL-13), and its prevalence has been increasing worldwide. Ferroptosis, a...
Th2-high asthma is characterized by elevated levels of type 2 cytokines, such as interleukin 13 (IL-13), and its prevalence has been increasing worldwide. Ferroptosis, a recently discovered type of programmed cell death, is involved in the pathological process of Th2-high asthma; however, the underlying mechanisms remain incompletely understood. In this study, we demonstrated that the serum level of malondialdehyde (MDA), an index of lipid peroxidation, positively correlated with IL-13 level and negatively correlated with the predicted forced expiratory volume in 1 s (FEV1%) in asthmatics. Furthermore, we showed that IL-13 facilitates ferroptosis by upregulating of suppressor of cytokine signaling 1 (SOCS1) through analyzing immortalized airway epithelial cells, human airway organoids, and the ovalbumin (OVA)-challenged asthma model. We identified that signal transducer and activator of transcription 6 (STAT6) promotes the transcription of SOCS1 upon IL-13 stimulation. Moreover, SOCS1, an E3 ubiquitin ligase, was found to bind to solute carrier family 7 member 11 (SLC7A11) and catalyze its ubiquitinated degradation, thereby promoting ferroptosis in airway epithelial cells. Last, we found that inhibiting SOCS1 can decrease ferroptosis in airway epithelial cells and alleviate airway hyperresponsiveness (AHR) in OVA-challenged wide-type mice, while SOCS1 overexpression exacerbated the above in OVA-challenged IL-13-knockout mice. Our findings reveal that the IL-13/STAT6/SOCS1/SLC7A11 pathway is a novel molecular mechanism for ferroptosis in Th2-high asthma, confirming that targeting ferroptosis in airway epithelial cells is a potential therapeutic strategy for Th2-high asthma.
Topics: Animals; Humans; Mice; Amino Acid Transport System y+; Asthma; Disease Models, Animal; Epithelial Cells; Interleukin-13; Lung; Mice, Inbred BALB C; Ovalbumin; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling Proteins; Th2 Cells
PubMed: 38484644
DOI: 10.1016/j.redox.2024.103100 -
International Forum of Allergy &... Sep 2023Inotodiol has been proven to have antitumor, antiviral, anti-inflammatory, and antiallergic properties. This study investigated the immunomodulatory capability of...
BACKGROUND
Inotodiol has been proven to have antitumor, antiviral, anti-inflammatory, and antiallergic properties. This study investigated the immunomodulatory capability of inotodiol in allergic rhinitis (AR) mice.
METHODS
Forty BALB/c mice were divided into four groups, 10 mice each: control (CON), AR with phosphate-buffered saline (PBS) treatment (AR), inotodiol treatment (AR+Ino), and dexamethasone treatment (AR+Dex). Episodes of sneezing and nose rubbing were counted. Cytokines in nasal lavage fluid (NLF) and immunoglobulin in blood serum were measured. Nasal mucosae from each group were used for protein, reverse transcriptase-polymerase chain reaction (RT-PCR), and histological analyses. Splenocytes were cultured for evaluation of cytokine production in each group.
RESULTS
Symptoms of rubbing and sneezing improved in the group of AR+Ino and AR+Dex than in the AR. NLF in the AR+Ino and AR+Dex also showed a significant decrease in interleukin (IL)-5, IL-10, and IL-13 compared to the AR. In addition, the number of eosinophils, goblet cells, and mast cells were notably lower in the nasal mucosae of the AR+Ino and AR+Dex. IL-4 and IL-17A in the AR+Ino and AR+Dex groups were decreased compared to the AR. Chemokines related to mast cell degradation were also decreased in the AR+Ino and AR+Dex groups. Total immunoglobulin (Ig)E, specific IgE and ovalbumin (OVA)-specific IgG1, and histamine levels were also significantly lower in the AR+Ino and AR+Dex groups. IL-10 and IL-13 were notably increased in the splenocytes of the AR after OVA stimulation, whereas the other groups showed no change.
CONCLUSION
These results indicate inotodiol can help suppress allergic responses by immunomodulation activities.
Topics: Animals; Mice; Interleukin-10; Interleukin-13; Sneezing; Rhinitis, Allergic; Inflammation; Nasal Mucosa; Cytokines; Immunoglobulin E; Mice, Inbred BALB C; Disease Models, Animal; Ovalbumin
PubMed: 36579475
DOI: 10.1002/alr.23121 -
Biochemical and Biophysical Research... Sep 2023This study aimed to establish the radio-immune imaging protocol on the basis of Avidin/Biotin system. The programmed death-ligand 1 (PD-L1) antibody (Atezolizumab) was...
This study aimed to establish the radio-immune imaging protocol on the basis of Avidin/Biotin system. The programmed death-ligand 1 (PD-L1) antibody (Atezolizumab) was employed as the primary molecule in targeting PD-L1, and the two-step strategy, consisting of the first injection of Avidin-conjugated PD-L1 monoclonal antibody (Atezolizumab) and the second injection of 7.4 MBq Ga-Biotin with a 60 h interval, was then verified on the colon cancer-bearing mice. PET imaging was performed at 30, 90, 180 min to measure the standard uptake value and tumor to liver ratios. Cellular binding experiments and in vivo distribution showed that the conjugation of Avidin did not affect the affinity of Atezolizumab to PD-L1 antigen. Biotin was radio-labeled with Ga with radiolabeling efficiency of 70.5 ± 3.5% and purification was needed to increase the radiochemical purity. For PD-L1-positive tumors, SUV was 0.38 ± 0.06 in the Avidin-Atezolizumab pre-treated mice at 90 min; the tumor/liver ratios of pre-targeting group were 1.06 ± 0.19 and 0.97 ± 0.16 at 30 and 90 min, while the absence of pre-treatment of Avidin was of the lower ratios as 0.88 ± 0.01 and 0.54 ± 0.11 when Ga-Biotin served as the radiopharmaceutical as well. In conclusion, pre-targeting immunoPET strategy can elevate the target-to-nontarget ratio, decrease the blood background and shorten the interval between injection of radiopharmaceuticals and PET scan, providing a highly PD-L1-specific and sensitive imaging method for the detection of tumorous immune micro-environment.
Topics: Mice; Animals; Biotin; Avidin; B7-H1 Antigen; Gallium Radioisotopes; Positron-Emission Tomography; Colonic Neoplasms; Radiopharmaceuticals; Cell Line, Tumor; Tumor Microenvironment
PubMed: 37354656
DOI: 10.1016/j.bbrc.2023.06.059 -
European Journal of Pharmacology Jul 2023Empagliflozin, a selective inhibitor of Na-glucose cotransporter-2, has been reported to exert anti-inflammatory and anti-fibrotic effects in addition to autophagy...
Empagliflozin, a selective inhibitor of Na-glucose cotransporter-2, has been reported to exert anti-inflammatory and anti-fibrotic effects in addition to autophagy modulation. Addressing the role of autophagy in allergic asthma revealed controversial results. The potential effect of empagliflozin treatment on airway inflammation and remodelling as well as autophagy modulation in a murine model of allergic asthma was investigated. Over a 7-week period, male BALB/c mice were sensitized and challenged by intraperitoneal injection and inhalation of ovalbumin, respectively. Animals were treated with empagliflozin (10 mg/kg; orally) and/or rapamycin (an autophagy inducer; 4 mg/kg; intraperitoneally) before every challenge. Methacholine-induced airway hyperresponsiveness was evaluated one day after the last challenge. After euthanasia, serum, bronchoalveolar lavage fluid, and lung tissues were collected for biochemical, histopathological, and immunohistochemical assessment. Results revealed that empagliflozin decreased airway hyperresponsiveness, serum ovalbumin-specific immunoglobulin E, and bronchoalveolar lavage total and differential leukocytic counts. Levels of inflammatory and profibrotic cytokines (IL-4, IL-5, IL-13, IL-17, and transforming growth factor-β1) were all inhibited. Moreover, empagliflozin preserved pulmonary microscopic architecture and alleviated bronchiolar epithelial thickening, goblet cell hyperplasia, fibrosis and smooth muscle hypertrophy. These effects were associated with inhibition of ovalbumin-activated autophagic flux, as demonstrated by decreased LC3B expression and LC3BII/I ratio, as well as increased P62 expression. However, the therapeutic potential of empagliflozin was inhibited when rapamycin was co-administered. In conclusion, this study demonstrates that empagliflozin has immunomodulatory, anti-inflammatory, and anti-remodelling properties in ovalbumin-induced allergic asthma and suggests that autophagic flux inhibition may play a role in empagliflozin's anti-asthmatic effects.
Topics: Male; Animals; Mice; Ovalbumin; Asthma; Lung; Bronchoalveolar Lavage Fluid; Respiratory Hypersensitivity; Inflammation; Cytokines; Anti-Inflammatory Agents; Autophagy; Mice, Inbred BALB C; Disease Models, Animal
PubMed: 37044313
DOI: 10.1016/j.ejphar.2023.175701