scholarly journals Free Feeding of CpG-Oligodeoxynucleotide Particles Prophylactically Attenuates Allergic Airway Inflammation and Hyperresponsiveness in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Takuma Okajima ◽  
Suguru Shigemori ◽  
Fu Namai ◽  
Tasuku Ogita ◽  
Takashi Sato ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Oral Delivery ◽  
Allergic Airway Inflammation ◽  
Fecal Microbiota ◽  
Attractive Alternative ◽  
Cell Hyperplasia ◽  
Cpg Oligodeoxynucleotides ◽  
Cpg Oligodeoxynucleotide ◽  
Cpg Odns ◽  
Free Feeding

CpG-oligodeoxynucleotides (CpG-ODNs) constitute an attractive alternative for asthma treatment. However, very little evidence is available from studies on the oral administration of CpG-ODNs in animals. Previously, we developed acid-resistant particles (named ODNcap) as an oral delivery device for ODNs. Here, we showed that free feeding of an ODNcap-containing feed prophylactically attenuates allergic airway inflammation, hyperresponsiveness, and goblet cell hyperplasia in an ovalbumin-induced asthma model. Using transcriptomics-driven approaches, we demonstrated that injury of pulmonary vein cardiomyocytes accompanies allergen inhalation challenge, but is inhibited by ODNcap feeding. We also showed the participation of an airway antimicrobial peptide (Reg3γ) and fecal microbiota in the ODNcap-mediated effects. Collectively, our findings suggest that daily oral ingestion of ODNcap may provide preventive effects on allergic bronchopulmonary insults via regulation of mechanisms involved in the gut-lung connection.

Melatonin biosynthesis restored by CpG oligodeoxynucleotides attenuates allergic airway inflammation via regulating NLRP3 inflammasome

Life Sciences ◽  
2019 ◽  
Vol 239 ◽  
pp. 117067 ◽  
Author(s):  
Hui-Mei Wu ◽  
Qiu-Meng Xie ◽  
Cui-Cui Zhao ◽  
Juan Xu ◽  
Xiao-Yun Fan ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Nlrp3 Inflammasome ◽  
Allergic Airway Inflammation ◽  
Cpg Oligodeoxynucleotides

scholarly journals A Selective α7 Nicotinic Acetylcholine Receptor Agonist, PNU-282987, Attenuates ILC2s Activation and Alternaria-Induced Airway Inflammation

2021 ◽  
Vol 11 ◽  
Author(s):  
Fang Yuan ◽  
Lili Jiang ◽  
Qianyang Li ◽  
Leon Sokulsky ◽  
Yuanyuan Wanyan ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Treated Group ◽  
Lymphoid Cells ◽  
Eosinophil Infiltration ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Cell Hyperplasia ◽  
Isolated Lung ◽  
Airway Eosinophil Infiltration

BackgroundThe anti-inflammatory effect of an α7nAChR agonist, PNU-282987, has previously been explored in the context of inflammatory disease. However, the effects of PNU-282987 on type 2 innate lymphoid cells (ILC2s)-mediated allergic airway inflammation has not yet been established.AimsTo determine the effects of PNU-282987 on the function of ILC2s in the context of IL-33– or Alternaria Alternata (AA)– induced airway inflammation.MethodsPNU-282987 was administered to mice that received recombinant IL-33 or AA intranasal challenges. Lung histological analysis and flow cytometry were performed to determine airway inflammation and the infiltration and activation of ILC2s. The previously published α7nAChR agonist GTS-21 was employed as a comparable reagent. ILC2s were isolated from murine lung tissue and cultured in vitro in the presence of IL-33, IL-2, and IL-7 with/without either PNU-282987 or GTS-21. The expression of the transcription factors GATA3, IKK, and NF-κB were also determined.ResultsPNU-282987 and GTS-21 significantly reduced goblet cell hyperplasia in the airway, eosinophil infiltration, and ILC2s numbers in BALF, following IL-33 or AA challenge. In vitro IL-33 stimulation of isolated lung ILC2s showed a reduction of GATA3 and Ki67 in response to PNU-282987 or GTS-21 treatments. There was a significant reduction in IKK and NF-κB phosphorylation in the PNU-282987–treated group when compared to the GTS-21–treated ILC2s.ConclusionPNU-282987 inhibits ILC2-associated airway inflammation, where its effects were comparable to that of GTS-21.

scholarly journals Enhanced Goblet Cell Hyperplasia in HDC Knockout Mice with Allergic Airway Inflammation

2009 ◽  
Vol 58 (1) ◽  
pp. 125-134 ◽  
Author(s):  
Kohei Yamauchi ◽  
Hong Mei Piao ◽  
Toshihide Nakadate ◽  
Toshiki Shikanai ◽  
Yutaka Nakamura ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Goblet Cell ◽  
Knockout Mice ◽  
Allergic Airway Inflammation ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia

scholarly journals Sevoflurane Inhibits the Th2 Response and NLRP3 Expression in Murine Allergic Airway Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Lixia Wang ◽  
Binshan Zha ◽  
Qiying Shen ◽  
Hongyun Zou ◽  
Cheng Cheng ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Inflammatory Cell ◽  
Allergic Airway Inflammation ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Th2 Response ◽  
Cell Hyperplasia ◽  
Mucus Production ◽  
Caspase 1 ◽  
Nlrp3 Expression

Background. Our colleagues have demonstrated an impressive therapeutic role of sevoflurane in a murine allergic airway inflammation model, but the mechanisms underlying this effect remain undefined. In this study, we tried to investigate the effect of sevoflurane on the resolution of allergic airway inflammation and to assess whether NLRP3 or the NLRP3 inflammasome is involved in this process. Methods. Female (C57BL/6) mice were sensitized and challenged with ovalbumin (OVA). Then, some of the mice received MCC950 (10 mg/kg; i.p.) or 3% sevoflurane. Total and differential inflammatory cell numbers, proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), the peribronchial inflammation density, and mucus production were evaluated. In addition, we analysed the protein levels of NLRP3, the apoptosis-associated speck-like protein containing the caspase activation and recruitment domain (ASC), pro-caspase-1, and caspase-1 in the lung tissue. Results. We found that OVA-induced inflammatory cell recruitment to peribronchial regions, goblet cell hyperplasia, the serum levels of IgE, inflammatory cells, and the Th2 cytokine secretion in BALF was potently suppressed by sevoflurane with an efficacy comparable with that suppressed by MCC950 treatment. Furthermore, sevoflurane, similar to MCC950, clearly inhibited the OVA-induced activity of NLRP3 in the lungs. In addition, we found that OVA challenge failed to increase the expression of ASC, pro-caspase-1, and caspase-1 in the lungs and the levels of IL-18 and IL-1β in BALF. Conclusion. Taken together, our data showed that sevoflurane ameliorated allergic airway inflammation by inhibiting Th2 responses and NLRP3 expression. The NLRP3 independent of inflammasomes participated in the pathogenesis of allergic asthma in this model.

scholarly journals Toll-Like Receptor 21 of Chicken and Duck Recognize a Broad Array of Immunostimulatory CpG-oligodeoxynucleotide Sequences

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 639
Author(s):  
Yu-Chen Chuang ◽  
Jen-Chih Tseng ◽  
Jing-Xing Yang ◽  
Yi-Ling Liu ◽  
Da-Wei Yeh ◽  
...  
Keyword(s):  
Nucleotide Sequence ◽  
Mammalian Cells ◽  
Cpg Odn ◽  
Toll Like Receptor ◽  
Cpg Oligodeoxynucleotides ◽  
Sequence Recognition ◽  
Cpg Oligodeoxynucleotide ◽  
Cpg Odns ◽  
Specific Activities ◽  
Species Specific

CpG-oligodeoxynucleotides (CpG-ODNs) mimicking the function of microbial CpG-dideoxynucleotides containing DNA (CpG-DNA) are potent immune stimuli. The immunostimulatory activity and the species-specific activities of a CpG-ODN depend on its nucleotide sequence properties, including CpG-hexamer motif types, spacing between motifs, nucleotide sequence, and length. Toll-like receptor (TLR) 9 is the cellular receptor for CpG-ODNs in mammalian species, while TLR21 is the receptor in avian species. Mammalian cells lack TLR21, and avian cells lack TLR9; however, both TLRs are expressed in fish cells. While nucleotide sequence properties required for a CpG-ODN to strongly activate mammalian TLR9 and its species-specific activities to different mammalian TLR9s are better studied, CpG-ODN activation of TLR21 is not yet well investigated. Here we characterized chicken and duck TLR21s and investigated their activation by CpG-ODNs. Chicken and duck TLR21s contain 972 and 976 amino acid residues, respectively, and differ from TLR9s as they do not have an undefined region in their ectodomain. Cell-based TLR21 activation assays were established to investigate TLR21 activation by different CpG-ODNs. Unlike grouper TLR21, which was preferentially activated by CpG-ODN with a GTCGTT hexamer motif, chicken and duck TLR21s do not distinguish among different CpG-hexamer motifs. Additionally, these two poultry TLR21s were activated by CpG-ODNs with lengths ranging from 15 to 31 nucleotides and with different spacing between CpG-hexamer motifs. These suggested that compared to mammalian TLR9 and grouper TLR21, chicken and duck TLR21s have a broad CpG-ODN sequence recognition profile. Thus, they could also recognize a wide array of DNA-associated molecular patterns from microbes. Moreover, CpG-ODNs are being investigated as antimicrobial agents and as vaccine adjuvants for different species. This study revealed that there are more optimized CpG-ODNs that can be used in poultry farming as anti-infection agents compared to CpG-ODN choices available for other species.

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