Exploring the mechanism of 6PPD/6PPD-Q-induced allergic rhinitis based on network toxicology, molecular docking, and molecular dynamic simulation
- 1Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Guangxi Medical University
Abstract
N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and its ozonated derivative, 6PPD-quinone (6PPD-Q), are tire-derived contaminants with established aquatic toxicity, yet their role in respiratory allergies like Allergic Rhinitis (AR) remains unclear. This study employs an integrative computational approach combining toxicological profiling, network pharmacology, and molecular dynamics (MD) simulations to elucidate their allergenic mechanisms. Potential targets were identified from multiple databases and intersected with AR-associated genes. Toxicological modeling revealed that both compounds pose significant respiratory and cutaneous sensitization risks, with 6PPD-Q exhibiting notable genotoxicity. Network analysis prioritized PTPRC (CD45), CXCL8, CCL2, TNF, and AKT1 as central hub targets. Functional enrichment indicated that these pollutants may disrupt leukocyte chemotaxis and activate key inflammatory pathways, including IL-17, NF-kappa B, and Fc epsilon RI signaling. MD simulations suggested stable binding of both pollutants within the PTPRC active site; notably, 6PPD-Q was associated with more pronounced conformational changes in the receptor, suggesting a potential for stronger immunomodulatory effects that warrants experimental investigation. This study provides mechanistic insight offers computational insights into how 6PPD and 6PPD-Q could contribute to mucosal immune dysregulation and may promote AR pathogenesis through multi-target actions, providing a preliminary foundation for environmental risk assessment and safer tire additive design.
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BibTeX
@article{wang2026exploring,
title = {{Exploring the mechanism of 6PPD/6PPD-Q-induced allergic rhinitis based on network toxicology, molecular docking, and molecular dynamic simulation}},
author = {Xuesong Wang and Jingyu Li and Nan Shi and Xia Zhu and Wei Xia and Anzhou Tang},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-62984-4},
url = {https://doi.org/10.1038/s41598-026-62984-4},
note = {CC BY},
}
RIS
TY - JOUR
TI - Exploring the mechanism of 6PPD/6PPD-Q-induced allergic rhinitis based on network toxicology, molecular docking, and molecular dynamic simulation
AU - Xuesong Wang
AU - Jingyu Li
AU - Nan Shi
AU - Xia Zhu
AU - Wei Xia
AU - Anzhou Tang
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-62984-4
UR - https://doi.org/10.1038/s41598-026-62984-4
AB - N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and its ozonated derivative, 6PPD-quinone (6PPD-Q), are tire-derived contaminants with established aquatic toxicity, yet their role in respiratory allergies like Allergic Rhinitis (AR) remains unclear. This study employs an integrative computational approach combining toxicological profiling, network pharmacology, and molecular dynamics (MD) simulations to elucidate their allergenic mechanisms. Potential targets were identified from multiple databases and intersected with AR-associated genes. Toxicological modeling revealed that both compounds pose significant respiratory and cutaneous sensitization risks, with 6PPD-Q exhibiting notable genotoxicity. Network analysis prioritized PTPRC (CD45), CXCL8, CCL2, TNF, and AKT1 as central hub targets. Functional enrichment indicated that these pollutants may disrupt leukocyte chemotaxis and activate key inflammatory pathways, including IL-17, NF-kappa B, and Fc epsilon RI signaling. MD simulations suggested stable binding of both pollutants within the PTPRC active site; notably, 6PPD-Q was associated with more pronounced conformational changes in the receptor, suggesting a potential for stronger immunomodulatory effects that warrants experimental investigation. This study provides mechanistic insight offers computational insights into how 6PPD and 6PPD-Q could contribute to mucosal immune dysregulation and may promote AR pathogenesis through multi-target actions, providing a preliminary foundation for environmental risk assessment and safer tire additive design.
SN - 2045-2322
ER -