Abstract
Rhinovirus infection frequently causes COPD and asthma exacerbations. Impaired anti-viral signaling and reduced viral clearance have both been seen in sick bronchial epithelium, potentially increasing exacerbations. Polyinosinic:polycytidylic acid (Poly(I:C)), a Toll-like receptor-3 (TLR3) ligand, has been shown to cause a viral exacerbation of severe asthma by detecting double-stranded RNA (dsRNA). The purpose of this work was to determine the effect of a TLR3/dsRNA complex inhibitor-Calbiochem drug in the prevention of Poly(I:C)-induced airway inflammation following TLR3 activation and to uncover a potential pathway for the cure of asthma through TLR3 inhibition. Mice were sensitized with Poly(I:C) as an asthma model before being challenged by PBS and ovalbumin (OVA) chemicals. The mice were administered a TLR3/dsRNA complex inhibitor. Throughout the trial, the mice’s body weight was measured after each dosage. Biochemical methods are used to analyze the protein as well as enzyme composition in airway tissues. BALF specimens are stained using Giemsa to identify inflammatory cells and lung histopathology to determine morphological abnormalities in lung tissues. By using the ELISA approach, cytokine levels such as TNF-α, IL-13, IL-6, IL-5, and IgE antibody expression in lung tissue and blood serum were assessed. TLR3/dsRNA complex inhibitor drug significantly lowered the number of cells in BALF and also on Giemsa staining slides. It also downregulated the level of TNF-α and IL-6 in contrast to OVA and Poly(I:C) administered in animals. A TLR3/dsRNA complex inhibitor decreased the fraction of oxidative stress markers (MDA, GSH, GPx, and CAT) in lung tissues while keeping the mice’s body weight constant during the treatment period. By decreasing alveoli, bronchial narrowing, smooth muscle hypertrophy, and granulocyte levels, the TLR3/dsRNA complex blocker significantly reduced the histopathological damage caused by OVA and Poly(I:C) compounds. In an animal model utilizing ovalbumin, TLR3/dsRNA complex inhibitors similarly reduced the bronchial damage produced by Poly(I:C). A novel TLR3/dsRNA complex inhibitor is expected to be employed in clinical studies since it suppresses airway inflammation without inducing antiviral approach resistance.
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All of the analyzed data and resources utilized in this publication were created during the examination of the experimental effort.
Abbreviations
- BALF:
-
Bronchoalveolar-lavage fluid
- DEX:
-
Dexamethasone
- DLC:
-
Differential leukocyte count
- dsRNA:
-
Double-stranded RNA
- ELISA:
-
Enzyme-linked immunosorbent assay
- ILs:
-
Interleukins
- OVA:
-
Ovalbumin
- Poly(I:C):
-
Polyinosinic:polycytidylic acid
- TNF- α:
-
Tumor necrosis factor
- ROS:
-
Reactive oxygen species
- TLC:
-
Total leukocyte count
- TLR:
-
Toll-like receptor
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Acknowledgements
Amity University, Noida, helped the authors with internet connectivity, journal availability, and research guidance, and we are grateful. Moreover, we acknowledge R.V. Northland Institute of Pharmacy for enabling the laboratory experiment with research resources that were needed. Furthermore, we acknowledge PRISAL Foundation (Pharmaceutical Royal International Society), India, for support in research guidance and supervision.
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Swamita Arora: conceptualization, methodology, software, data curation, visualization, investigation, writing — original draft preparation. Sangeetha Gupta: conceptualization, methodology, visualization, investigation, supervision. Wasim Akram: conceptualization, visualization, investigation, supervision, writing — review and editing. Ahmed E. Altyar: visualization, reviewing, and editing. Priti Tagde: data curation, visualization, writing — reviewing, editing, and supervision. All authors read and approved the final version of the manuscript.
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To verify the validity of the experimental findings, only 6 mice per group were used per ethical standards, and the tests were conducted by methods approved by R.V. Northland Institute’s Animal Institutional Ethical Committee (no. 1149/PO/Re/S/07/CPCSEA). The animals’ development, health, and capacity for food intake were tracked during the whole trial time to ensure their overall wellbeing.
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Arora, S., Gupta, S., Akram, W. et al. Effect of TLR3/dsRNA complex inhibitor on Poly(I:C)-induced airway inflammation in Swiss albino mice. Environ Sci Pollut Res 30, 28118–28132 (2023). https://doi.org/10.1007/s11356-022-23987-6
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DOI: https://doi.org/10.1007/s11356-022-23987-6