RESUMO
Allergic asthma is a complex inflammatory disorder predominantly orchestrated by T helper 2 (Th2) lymphocytes. The anti-inflammatory protein Clara Cell 10-kDa (CC10), also known as secretoglobin family 1A member 1 (SCGB1A1), shows promise in modulating respiratory diseases. However, its precise role in asthma remains unclear. This study examines the potential of CC10 to suppress allergic asthma inflammation, specifically assessing its regulatory effects on Th2 cell responses and dendritic cells (DCs). Lower CC10 levels in asthma were observed and correlated with increased IgE and lymphocytes. Cc10-/- mice exhibited exacerbated allergic airway inflammation marked by increased inflammatory cell infiltration, Th2 cytokines, serum antigen-specific IgE levels, and airway hyperresponsiveness (AHR) in house dust mite (HDM)-induced models. Conversely, recombinant CC10 significantly attenuated these inflammatory responses. Intriguingly, CC10 did not directly inhibit Th cell activation but significantly downregulated the population of CD11b+CD103- DCs subsets in lungs of asthmatic mice and modulated the immune activation functions of DCs through NF-κB signaling pathway. The mixed lymphocyte response assay revealed that DCs mediated the suppressive effect of CC10 on Th2 cell responses. Collectively, CC10 profoundly mitigates Th2-type allergic inflammation in asthma by modulating lung DC phenotype and functions, highlighting its therapeutic potential for inflammatory airway conditions and other related immunological disorders.
Assuntos
Asma , Células Dendríticas , Pulmão , Células Th2 , Uteroglobina , Animais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Asma/imunologia , Asma/patologia , Células Th2/imunologia , Células Th2/metabolismo , Uteroglobina/genética , Uteroglobina/metabolismo , Camundongos , Pulmão/patologia , Pulmão/imunologia , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Inflamação/patologia , Inflamação/imunologia , Inflamação/metabolismo , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Pyroglyphidae/imunologia , NF-kappa B/metabolismo , Citocinas/metabolismo , Feminino , Camundongos Endogâmicos BALB CRESUMO
Understanding how stress hormones induce apoptosis in oviductal epithelial cells (OECs) and mural granulosa cells (MGCs) can reveal the mechanisms by which female stress impairs embryonic development and oocyte competence. A recent study showed that tissue plasminogen activator (tPA) ameliorates corticosterone-induced apoptosis in MGCs and OECs by acting on its receptors low-density lipoprotein receptor-related protein 1 (LRP1) and Annexin A2 (ANXA2), respectively. However, whether tPA is involved in corticotropin-releasing hormone (CRH)-induced apoptosis and whether it uses the same or different receptors to inhibit apoptosis induced by different hormones in the same cell type remains unknown. This study showed that CRH triggered apoptosis in both OECs and MGCs and significantly downregulated tPA expression. Moreover, tPA inhibits CRH-induced apoptosis by acting on ANXA2 in both OECs and MGCs. While ANXA2 inhibits apoptosis via phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling, LRP1 reduces apoptosis via mitogen-activated protein kinase (MAPK) signaling. Thus, tPA used the same receptor to inhibit CRH-induced apoptosis in both OECs and MGCs, however used different receptors to inhibit corticosterone-induced apoptosis in MGCs and OECs. These data helps understand the mechanism by which female stress impairs embryo/oocyte competence and proapoptotic factors trigger apoptosis in different cell types.
Assuntos
Apoptose , Hormônio Liberador da Corticotropina , Células Epiteliais , Células da Granulosa , Ativador de Plasminogênio Tecidual , Animais , Feminino , Apoptose/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Camundongos , Ativador de Plasminogênio Tecidual/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Hormônio Liberador da Corticotropina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Oviductos/metabolismo , Oviductos/efeitos dos fármacos , Anexina A2/metabolismo , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Tubas Uterinas/metabolismo , Tubas Uterinas/efeitos dos fármacosRESUMO
Transgelin-2 has been regarded as an actin-binding protein that induces actin gelation and regulates actin cytoskeleton. However, transgelin-2 has recently been shown to relax the myosin cytoskeleton of the airway smooth muscle cells by acting as a receptor for extracellular metallothionein-2. From a clinical perspective, these results support transgelin-2 as a promising therapeutic target for diseases such as cancer and asthma. The inhibition of transgelin-2 prevents actin gelation and thereby cancer cell proliferation, invasion, and metastasis. Conversely, the activation of transgelin-2 with specific agonists relaxes airway smooth muscles and reduces pulmonary resistance in asthma. Here, we review new studies on the biochemical properties of transgelin-2 and discuss their clinical implications for the treatment of immune, oncogenic, and respiratory disorders.
Assuntos
Asma/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Neoplasias/metabolismo , Actinas/metabolismo , Animais , Asma/tratamento farmacológico , Asma/patologia , Proliferação de Células/efeitos dos fármacos , Humanos , Proteínas dos Microfilamentos/agonistas , Proteínas dos Microfilamentos/antagonistas & inibidores , Proteínas Musculares/agonistas , Proteínas Musculares/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/patologiaRESUMO
GMrepo (data repository for Gut Microbiota) is a database of curated and consistently annotated human gut metagenomes. Its main purpose is to facilitate the reusability and accessibility of the rapidly growing human metagenomic data. This is achieved by consistently annotating the microbial contents of collected samples using state-of-art toolsets and by manual curation of the meta-data of the corresponding human hosts. GMrepo organizes the collected samples according to their associated phenotypes and includes all possible related meta-data such as age, sex, country, body-mass-index (BMI) and recent antibiotics usage. To make relevant information easier to access, GMrepo is equipped with a graphical query builder, enabling users to make customized, complex and biologically relevant queries. For example, to find (1) samples from healthy individuals of 18 to 25 years old with BMIs between 18.5 and 24.9, or (2) projects that are related to colorectal neoplasms, with each containing >100 samples and both patients and healthy controls. Precomputed species/genus relative abundances, prevalence within and across phenotypes, and pairwise co-occurrence information are all available at the website and accessible through programmable interfaces. So far, GMrepo contains 58 903 human gut samples/runs (including 17 618 metagenomes and 41 285 amplicons) from 253 projects concerning 92 phenotypes. GMrepo is freely available at: https://gmrepo.humangut.info.
Assuntos
Bases de Dados Genéticas , Microbioma Gastrointestinal , Metagenoma , Metagenômica/métodos , Software , Genes Bacterianos , Genoma Humano , Humanos , Anotação de Sequência MolecularRESUMO
Ezrin is a critical structural protein that organizes receptor complexes and orchestrates their signal transduction. In this study, we review the ezrin-meditated regulation of critical receptor complexes, including the epidermal growth factor receptor (EGFR), CD44, vascular cell adhesion molecule (VCAM), and the deleted in colorectal cancer (DCC) receptor. We also analyze the ezrin-meditated regulation of critical pathways associated with asthma, such as the RhoA, Rho-associated protein kinase (ROCK), and protein kinase A (cAMP/PKA) pathways. Mounting evidence suggests that ezrin plays a role in controlling airway cell function and potentially contributes to respiratory diseases. Ezrin can participate in asthma pathogenesis by affecting bronchial epithelium repair, T lymphocyte regulation, and the contraction of the airway smooth muscle cells. These studies provide new insights for the design of novel therapeutic strategies for asthma treatment.
Assuntos
Proteínas do Citoesqueleto/metabolismo , Células Epiteliais/fisiologia , Miócitos de Músculo Liso/fisiologia , Transdução de Sinais , Asma , Brônquios/citologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas do Citoesqueleto/fisiologia , Receptor DCC/metabolismo , Receptores ErbB/metabolismo , Humanos , Receptores de Hialuronatos/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
Two new xanthones smilone A (1), smilone B (2), and a new lignin smilgnin A (3) were isolated from the rhizomes of Smilax china L., together with three known xanthones (4-6), four lignins (7-10), two flavones (11, 12), two stilbenoids (13, 14), and ten organic phenoloids (15-24). Of them, compounds 4-6 were isolated from the genus Smilax for the first time. The structures of 1-24 were elucidated by the extensive analysis of spectral data and compared with the literature. All compounds were evaluated for their inhibitory effects against LPS-induced NO production in RAW264.7 macrophages. Among them, compound 24 exhibited significant inhibitory activity against NO production (IC50 = 1.26 µM), while compounds 3, 6, and 7 showed weak activities at the concentration of 50 µM.[Formula: see text].
Assuntos
Smilax , Xantonas , China , Lignina , Estrutura MolecularRESUMO
Airway hyperresponsiveness (AHR) is a major clinical problem in allergic asthma mainly caused by the hypercontractility of airway smooth muscles (ASM). S100A8 is an important member of the S100 calcium-binding protein family with a potential to regulate cell contractility. Here, we analyze the potential of S100A8 to regulate allergen-induced AHR and ASM contraction. Treatment with recombinant S100A8 (rS100A8) diminished airway hyperresponsiveness in OVA-sensitized rats. ASM contraction assays showed that rS100A8 reduced hypercontractility in both isolated tracheal rings and primary ASM cells treated by acetylcholine. rS100A8 markedly rescued the phosphorylation level of myosin light chain induced by acetylcholine in ASM cells. These results show that rS100A8 plays a protective role in regulating AHR in asthma by inhibiting ASM contraction. These results support S100A8 as a novel therapeutic target to control ASM contraction in asthma.
Assuntos
Calgranulina A/fisiologia , Músculo Liso/fisiologia , Hipersensibilidade Respiratória/prevenção & controle , Acetilcolina/administração & dosagem , Animais , Células Cultivadas , Contração Muscular/fisiologia , Cadeias Leves de Miosina/metabolismo , Ovalbumina/administração & dosagem , Fosforilação , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/farmacologiaRESUMO
BACKGROUND: Airway remodeling is a key feature of asthma, characterized by increased proliferation of airway smooth muscle cells (ASMCs). S100A8 is a calcium-binding protein with a potential to regulate cell proliferation. Here, the effect of exogenous S100A8 protein on the proliferation of ASMCs induced by platelet-derived growth factor (PDGF) and the underlying molecular mechanism was investigated. METHODS: Rat ASMCs were cultured with or without a neutralizing antibody to the receptor for advanced glycation end-products (RAGE), a potential receptor for S100A8 protein. Purified recombinant rat S100A8 protein was then added into the cultured cells, and the proliferation of ASMCs induced by PDGF was detected by colorimetric-based WST-8 assay and ampedance-based xCELLigence proliferation assay. The expression levels of RAGE in ASMCs were analyzed using western blotting assay. RESULTS: Results showed that exogenous S100A8 inhibited the PDGF-induced proliferation of rat ASMCs in a dose-dependent manner with the maximal effect at 1 µg/ml in vitro. Furthermore, when ASMCs was pre-treated with anti-RAGE neutralizing antibody, the inhibitory effect of S100A8 on PDGF-induced proliferation was significantly suppressed. In addition, neither the treatment with S100A8 or PDGF alone nor the pre-treatment with rS100A8 followed by PDGF stimulation affected the expression levels of RAGE. CONCLUSIONS: Our study demonstrated that S100A8 inhibits PDGF-induced ASMCs proliferation in a manner dependent on membrane receptor RAGE.
Assuntos
Calgranulina A/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/agonistas , Receptor para Produtos Finais de Glicação Avançada/efeitos dos fármacos , Animais , Células Cultivadas , RatosRESUMO
S100A8 is an important member of the S100 protein family, which is involved in intracellular and extracellular regulatory activities. We previously reported that the S100A8 protein was differentially expressed in the asthmatic respiratory tracts. To understand the potential role of S100A8 in asthma, we investigated the effect of recombinant S100A8 protein on the platelet-derived growth factor (PDGF)-induced migration of airway smooth muscle cells (ASMCs) and the underlying molecular mechanism by using multiple methods, such as impedance-based xCELLigence migration assay, transwell migration assays and wound-healing assays. We found that exogenous S100A8 protein significantly inhibited PDGF-induced ASMC migration. Furthermore, the migration inhibition effect of S100A8 was blocked by neutralizing antibody against the receptor for advanced glycation end-products (RAGE), a potential receptor for the S100A8 protein. These findings provide direct evidence that exogenous S100A8 protein inhibits the PDGF-induced migration of ASMCs through the membrane receptor RAGE. Our study highlights a novel role of S100A8 as a potential means of counteracting airway remodeling in chronic airway diseases.
Assuntos
Calgranulina A/fisiologia , Movimento Celular/fisiologia , Miócitos de Músculo Liso/fisiologia , Fator de Crescimento Derivado de Plaquetas/fisiologia , Receptor para Produtos Finais de Glicação Avançada/fisiologia , Traqueia/patologia , Traqueia/fisiologia , Animais , Anticorpos Neutralizantes , Asma/patologia , Asma/fisiopatologia , Calgranulina A/administração & dosagem , Calgranulina A/genética , Células Cultivadas , Modelos Animais de Doenças , Ratos , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Receptor para Produtos Finais de Glicação Avançada/imunologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , CicatrizaçãoRESUMO
BACKGROUND: BrdU is a commonly used reagent in cell proliferation assays, and WST-1 measurement is widely used to detect cell viability. However, no previous study has formally reported the combination of the two assays, which may be used to detect the proliferation and viability simultaneously. In this study, we examined the effect of adding BrdU 2 h prior to the WST-1 assay and tried to test the possibility of the combined detection using rat airway smooth muscle cells. RESULTS: The WST-1 measurements obtained from the combined detection were consistent with those obtained from the separate detection, which suggested that the addition of BrdU 2 h prior to the WST-1 analysis did not affect the WST-1 results. The BrdU measurements obtained from the combined detection also demonstrated the same trend as that obtained from the separate detection, and dosages of 200, 400 and 800 ng/ml testing reagent significantly inhibited the proliferation of rat airway smooth muscle cells. CONCLUSIONS: Our study suggests that the BrdU and WST-1 measurements can be applied simultaneously without mutual interference, which may increase the efficacy and consistency of these measurements to a certain extent.
Assuntos
Bromodesoxiuridina/farmacologia , Proliferação de Células/fisiologia , Miócitos de Músculo Liso/fisiologia , Avaliação da Tecnologia Biomédica/métodos , Sais de Tetrazólio/farmacologia , Traqueia/citologia , Animais , Calgranulina B/administração & dosagem , Sobrevivência Celular/fisiologia , Ensaio de Imunoadsorção Enzimática , Cultura Primária de Células , Ratos , Kit de Reagentes para Diagnóstico , Traqueia/crescimento & desenvolvimentoRESUMO
BACKGROUND: The total effects of adequate real acupuncture treatment consist of pathologic-specific and non-specific physiological effects. The latter may be the fundamental component of the therapeutic effects of acupuncture. This study investigated the physiological background effects of acupuncture in normal rats treated with acupuncture. METHODS: Manual acupuncture was performed on normal rats at experienced acupoints, GV14 (Dazhui), BL12 (Fengmen) and BL13 (Feishu), once every other day for two weeks. The proteomic profile of rat lung tissue was examined using 2-DE/MS-based proteomic techniques. Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were analyzed for differentially expressed proteins using the WebGestalt toolkit. RESULTS: In total, 25 differentially expressed protein spots were detected in the 2-DE gels. Among these spots, 24 corresponded to 20 unique proteins that were successfully identified using mass spectrometry. Subsequent GO and KEGG pathway analyses demonstrated that these altered proteins were mainly involved in biological processes, such as 'protein stabilization', 'glycolysis/gluconeogenesis' and 'response to stimulus'. CONCLUSIONS: Our study indicated the non-specific background effects of acupuncture at acupoints GV14, BL12 and BL13 likely maintained internal homeostasis via regulation of the local stimulus response, energy metabolism, and biomolecule function balance, which may be important contributors to the therapeutic effects of acupuncture.
Assuntos
Terapia por Acupuntura , Pulmão/metabolismo , Proteoma/análise , Proteoma/fisiologia , Pontos de Acupuntura , Animais , Masculino , Proteínas/análise , Proteínas/classificação , Proteômica , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: The dosage of ovalbumin (OVA) during the sensitization stage is considered a crucial factor in the development of airway hyperresponsiveness (AHR). However, the inconsistent dosages of sensitizing OVA used in current studies and the lack of research on their impact on AHR are notable limitations. METHODS: We examined the impact of increasing sensitizing doses of OVA in a murine asthma model, which entailed initial sensitization with OVA followed by repeated exposure to OVA aerosols. BALB/c mice were primed with doses of OVA (0, 10, 20, 50, and 100 µg) plus 1 mg Alum on Days 0 and 7, and were challenged with OVA aerosols (10 mg/mL for 30 min) between Days 14 and 17. Antigen-induced AHR to methacholine (MCh), as well as histological changes, eosinophilic infiltration, and epithelial injury were assessed. RESULTS: The result indicated that there are striking OVA dose-related differences in antigen-induced AHR to MCh. The most intense antigen-induced AHR to MCh was observed with sensitization at 50 µg, while weaker responses were seen at 10, 20, and 100 µg. Meanwhile, there was a significant increase in eosinophil count with sensitization at 50 µg. The changes of AHR were correlated with total cells count, lymphocytes count, eosinophils count, and basophils count in bronchoalveolar lavage fluid; however, it did not correlate with histological changes such as cellular infiltration into bronchovascular bundles and goblet cell hyperplasia of the bronchial epithelium. CONCLUSION: Overall, this study demonstrated that sensitization with 50 µg of OVA resulted in the most significant AHR compared to other dosages. These findings may offer valuable insights for future research on mouse asthma modeling protocols.
Assuntos
Asma , Hiper-Reatividade Brônquica , Hipersensibilidade Respiratória , Animais , Camundongos , Ovalbumina , Aerossóis e Gotículas Respiratórios , Asma/patologia , Cloreto de MetacolinaRESUMO
IMPORTANCE: Phage therapy is gaining traction as an alternative to antibiotics due to the rise of multi-drug-resistant (MDR) bacteria. This study assessed the pharmacokinetics and safety of PA_LZ7, a phage targeting MDR Pseudomonas aeruginosa, in mice. After intravenous administration, the phage showed an exponential decay in plasma and its concentration dropped significantly within 24 h for all dosage groups. Although there was a temporary increase in certain plasma cytokines and spleen weight at higher dosages, no significant toxicity was observed. Therefore, PA_LZ7 shows potential as an effective and safe candidate for future phage therapy against MDR P. aeruginosa infections.
Assuntos
Bacteriófagos , Infecções por Pseudomonas , Fagos de Pseudomonas , Animais , Camundongos , Fagos de Pseudomonas/genética , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Infecções por Pseudomonas/terapia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosaRESUMO
The WST-1 assay is an efficient test for cell viability measurement and the standard incubation time is 2h. In order to test if one-time addition of WST-1 reagent can reflect the relative cell viability trend of the testing agents at different time points, the effects of 2h standard incubation time and long term incubation time (2h+24h, 2h+48h) of WST-1 were compared in the rat airway smooth muscle cells (ASM cells) after adding of the testing protein MRP-14. Our study demonstrated that the effect of different dosages of the protein after 2h WST-1 incubation on ASM cells showed a tendency of inhibition and achieved the maximal inhibition effect at 72h. The relative cell viability trend of the 2h+24h group was the same to that of the 2h WST-1 incubation, which means that 24h prolonged incubation time of WST-1 reagent could still reflect the relative cell viability trend. In conclusion, the study suggested that the WST-1 is a proper candidate reagent for continuous monitation of cell viability.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Pulmão , Miócitos de Músculo Liso/efeitos dos fármacos , Sais de Tetrazólio/administração & dosagem , Animais , Calgranulina B/metabolismo , Sobrevivência Celular/fisiologia , Pulmão/citologia , Pulmão/efeitos dos fármacos , RatosRESUMO
Although studies indicate that female stress-increased secretion of glucocorticoids impairs oocyte competence and embryo development, by inducing apoptosis of ovarian and oviductal cells, respectively, the mechanisms by which glucocorticoids induce apoptosis of ovarian and oviductal cells are largely unclear. Tissue plasminogen activator (tPA) has been involved in apoptosis of different cell types. However, while some studies indicate that tPA is proapoptotic, others demonstrate its antiapoptotic effects. This study has explored the role and action mechanisms of tPA in corticosterone-induced apoptosis of mouse mural granulosa cells (MGCs) and oviductal epithelial cells (OECs). The results demonstrate that culture with corticosterone significantly increased apoptosis, while decreasing levels of tPA (Plat) mRNA and tPA protein in both MGCs and OECs. Culture with tPA ameliorated corticosterone-induced apoptosis of MGCs and OECs. Furthermore, while tPA protected MGCs from corticosterone-induced apoptosis by interacting with low-density lipoprotein receptor-related protein 1 (LRP1), it protected OECs from the apoptosis by acting on Annexin 2 (ANXA2). In conclusion, tPA is antiapoptotic in both MGCs and OECs, and it protects MGCs and OECs from corticosterone-induced apoptosis by interacting with LRP1 and ANXA2, respectively, suggesting that tPA may use different receptors to inhibit apoptosis in different cell types.
Assuntos
Corticosterona , Glucocorticoides , Animais , Feminino , Camundongos , Apoptose , Corticosterona/farmacologia , Células Epiteliais/metabolismo , Glucocorticoides/farmacologia , Ativador de Plasminogênio Tecidual/metabolismoRESUMO
Asthma is a complex and heterogeneous respiratory disease that causes serious social and economic burdens. Current drugs such as ß2-agonists cannot fully control asthma. Our previous study found that Transgelin-2 is a potential target for treating asthmatic pulmonary resistance. Herein, we discovered a zolinium compound, TSG1180, that showed a strong interaction with Transgelin-2. The equilibrium dissociation constants (KD) of TSG1180 to Transgelin-2 were determined to be 5.363 × 10-6 and 9.81 × 10-6 M by surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Cellular thermal shift assay (CETSA) results showed that the thermal stability of Transgelin-2 increased after coincubation of TSG1180 with lysates of airway smooth muscle cells (ASMCs). Molecular docking showed that Arg39 may be the key residue for the binding. Then, the SPR result showed that the binding affinity of TSG1180 to Transgelin-2 mutant (R39E) was decreased by 1.69-fold. Real time cell analysis (RTCA) showed that TSG1180 treatment could relax ASMCs by 19 % (P < 0.05). Once Transgelin-2 was inhibited, TSG1180 cannot induce a relaxation effect, suggesting that the relaxation effect was specifically mediated by Transgelin-2. In vivo study showed TSG1180 effectively reduced pulmonary resistance by 64 % in methacholine-induced mice model (P < 0.05). Furthermore, the phosphorylation of Ezrin at T567 was increased by 8.06-fold, the phosphorylation of ROCK at Y722 was reduced by 38 % and the phosphorylation of RhoA at S188 was increased by 52 % after TSG1180 treatment. These results suggested that TSG1180 could be a Transgelin-2 agonist for further optimization and development as an anti-asthma drug.
Assuntos
Asma , Camundongos , Animais , Simulação de Acoplamento Molecular , Asma/tratamento farmacológico , Asma/metabolismo , Pulmão , Proteínas dos Microfilamentos/metabolismo , Miócitos de Músculo Liso/metabolismoRESUMO
Although the beneficial effects of acupuncture in asthma treatment have been well documented, little is known regarding the biological basis of this treatment. Changes in the lung proteome of acupuncture-treated rats with asthma onset were comparatively analyzed using a two-dimensional gel electrophoresis (2DE) and mass-spectrometry- (MS-) based proteomic approach. Acupuncture on specific acupuncture points appeared to improve respiratory function and reduce the total number of leukocytes and eosinophils in bronchoalveolar lavage fluid in OVA-induced asthma onset. Image analysis of 2DE gels revealed 32 differentially expressed acupuncture-specific protein spots in asthma onset; 30 of which were successfully identified as 28 unique proteins using LC-MS/MS. Bioinformatic analyses indicated that these altered proteins are most likely involved in inflammation-related biological functions, and the functional associations of these proteins result in an inflammation signaling pathway. Acupuncture regulates the pathway at different levels by regulating several key nodal proteins, including downregulating of proinflammatory proteins (e.g., S100A8, RAGE, and S100A11) and upregulating of anti-inflammatory proteins (e.g., CC10, ANXA5, and sRAGE). These deregulated inflammation-related proteins may mediate, at least in part, the antiasthmatic effect of acupuncture. Further functional investigation of these acupuncture-specific effector proteins could identify new drug candidates for the prophylaxis and treatment of asthma.
RESUMO
S100A8, an important member of the S100 protein family, is a low-molecular-weight (10.8 kDa) calcium-binding protein containing conserved EF-hand structural motifs. Previous studies have shown that the biological function of S100A8 protein is associated with a variety of inflammatory diseases, for example asthma. S100A8 protein plays important roles in the regulation of inflammation. It can activate inflammatory cells and cytokines via chemotactic activity for neutrophils, and bind to the receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4), thus mediating intracellular inflammatory signaling transduction. Additionally, recent studies have reported the anti-inflammation activity of S100A8 protein, which indicates that S100A8 may have a more complex function of biological regulation in the different pathophysiological conditions. In this review, we summarized the studies on the functions and molecular mechanisms of S100A8 protein in inflammation, which would propose a novel strategy for the prophylaxis and treatment of asthma and other inflammatory diseases.
Assuntos
Asma/fisiopatologia , Calgranulina A/fisiologia , Inflamação/fisiopatologia , Animais , HumanosRESUMO
Traditional Chinese medicine (TCM) has been successfully used to treat asthmatic conditions for centuries. Nevertheless, the current hotspots and research frontiers on TCM for asthma have not been systematically investigated on the basis of bibliometric analysis. In this study, a scientometric analysis (1991-2021) was carried out on 3081 journal articles obtained from the Web of Science Core Collection database to explore the basic characteristics, research hotspots, and frontiers of TCM in asthma research. The results revealed the following: (1) Research on TCM in asthma has received widespread attention since the beginning of the 21st century; perhaps 2009 was an important turning point. TCM in asthma research shows a trend of interdisciplinary development. (2) Well-known universities/institutions in China, the United States, and South Korea have conducted the main body of current TCM research in asthma. JingCheng Dong (Fudan University, China) and XiuMin Li (Mount Sinai School of Medicine, USA) are the top 2 leading authors in this field. However, there is still a lack of international cooperation in the field of TCM in asthma research, and the influence of researchers in China and South Korea still needs improvement. (3) The Journal of Allergy and Clinical Immunology ranks first in the research field on the influence of TCM in asthma. (4) Hotspots and frontiers of TCM in asthma are provided according to the timeline analyses of the research. In the former, complementary medicine, alternative treatment, allergic rhinitis, airway remodeling, Dietary Approach to Stop Hypertension diet, and eosinophilic esophagitis are in the exploratory stage. In the latter, pharmacology, essential oil, gut microbiota, and oxidative stress were investigated from 2006 until late 2021 as period B, which contradicts period A (1991-2005). Moreover, limitations of this bibliometric analysis and the study of TCM research in asthma still exist, which are sufficiently important to warrant further investigations. Finally, we propose the significant importance of the real quintessence and characteristics of TCM in clinical and future research.
RESUMO
Dendritic cells (DCs) are efficient antigen-presenting cells that serve as a link between the innate and adaptive immune systems. These cells are broadly involved in cellular and humoral immune responses by presenting antigens to initiate T cell reactions, cytokine and chemokine secretion, T cell differentiation and expansion, B cell activation and regulation, and the mediation of immune tolerance. The functions of DCs depend on their activation status, which is defined by the stages of maturation, phenotype differentiation, and migration ability, among other factors. IL-6 is a soluble mediator mainly produced by a variety of immune cells, including DCs, that exerts pleiotropic effects on immune and inflammatory responses through interaction with specific receptors expressed on the surface of target cells. Here, we review the role of IL-6, when generated in an inflammatory context or as derived from DCs, in modulating the biologic function and activation status of DCs and emphasize the importance of searching for novel strategies to target the IL-6/IL-6 signaling pathway as a means to diminish the inflammatory activity of DCs in immune response or to prime the immunogenic activity of DCs in immunosuppressive conditions.