CpG-ODNs and Budesonide Act Synergistically to Improve Allergic Responses in Combined Allergic Rhinitis and Asthma Syndrome Induced by Chronic Exposure to Ovalbumin by Modulating the TSLP-DC-OX40L Axis.

Abstract

The experimental model of combined allergic rhinitis and asthma syndrome (CARAS) has shown that CpG oligodeoxynucleotides (CpG-ODNs) are potential inhibitors of type 2 helper cell-driven inflammatory responses. Currently available CpG-ODNs modestly inhibit allergic responses in CARAS, while a combination strategy for upper airway treatment by co-administration of CpG-ODNs and glucocorticoids may show good efficacy. This study aimed to assess the therapeutic effects of CpG-ODNs combined with budesonide (BUD) on upper and lower-airway inflammation and remodeling in mice with CARAS induced by chronic exposure to ovalbumin (OVA), exploring the possible underlying molecular mechanisms. A BALB/c mouse model of chronic CARAS was established by systemic sensitization and repeated challenge with OVA. Treatment with CpG-ODNs or BUD by intranasal administration was started 1 h after OVA challenge. Then, nasal mucosa and lung tissues were fixed and stained for pathologic analysis. The resulting immunologic variables and TSLP-DC-OX40L axis parameters were evaluated. Both CpG-ODNs and BUD intranasal administration are effective on reducing Th2-type airway inflammation and tissue remodeling. Co-administration of CpG-ODNs and BUD was more effective than each monotherapy in attenuating upper and lower-airway inflammation as well as airway remodeling in chronic CARAS. Notably, combination of CpG-ODNs with BUD modulated the TSLP-DC-OX40L axis, as demonstrated by decreased TSLP production in the nose and lung, alongside decreased TSLPR and OX40L in DC. Intranasal co-administration of CpG-ODNs and BUD synergistically alleviates airway inflammation and tissue remodeling in experimental chronic CARAS, through shared cellular pathways, as a potent antagonist of the TSLP-DC-OX40L axis.

• Authors: Hong-Tao Li, Zhuang-Gui Chen, Yu-Sen Lin, Hui Liu, Jin Ye, Xiao-Ling Zou, Yan-Hong Wang, Hai-Ling Yang, Tian-Tuo Zhang
• Journal: Inflammation (Inflammation) Vol. 41 Issue 4 Pg. 1304-1320 (Aug 2018) ISSN: 1573-2576 [Electronic] United States
• PMID: 29654433 (Publication Type: Journal Article)

Chemical References

• CPG-oligonucleotide
• Cytokines
• Membrane Glycoproteins
• OX40 Ligand
• Oligodeoxyribonucleotides
• Tnfsf4 protein, mouse
• Tumor Necrosis Factor Inhibitors
• Budesonide
• Ovalbumin
• Thymic Stromal Lymphopoietin
• TSLP protein, mouse

Topics

• Airway Remodeling (drug effects)
• Animals
• Asthma (drug therapy)
• Budesonide (pharmacology)
• Cytokines (antagonists & inhibitors)
• Drug Synergism
• Inflammation (drug therapy)
• Membrane Glycoproteins (antagonists & inhibitors)
• Mice
• Mice, Inbred BALB C
• OX40 Ligand
• Oligodeoxyribonucleotides (pharmacology)
• Ovalbumin (adverse effects)
• Rhinitis, Allergic (drug therapy)
• Tumor Necrosis Factor Inhibitors
• Thymic Stromal Lymphopoietin