Phosphopeptides P140 cause oxidative burst responses of pulmonary macrophages in an imiquimod-induced lupus model.
H3cit
Lupus
Macrophages
Neutrophils
ROS
Journal
Molecular biomedicine
ISSN: 2662-8651
Titre abrégé: Mol Biomed
Pays: Singapore
ID NLM: 9918283581406676
Informations de publication
Date de publication:
03 Nov 2023
03 Nov 2023
Historique:
received:
05
05
2023
accepted:
18
10
2023
medline:
3
11
2023
pubmed:
3
11
2023
entrez:
3
11
2023
Statut:
epublish
Résumé
Recent studies challenge the dogma that a 21-mer phosphopeptide P140 protects against direct cell damage in the phase-III clinical trial (NCT02504645) for lupus, involving reactive oxygen species (ROS)-dependent release of citrullinated histone H3 (H3cit)-linked neutrophil extracellular traps. An open question is the cellular location of ROS production and H3cit formation in lupus. In this study, we examined the effects of P140 peptides on ROS production and H3cit location in lupus with in vivo and situ fluorescence imaging with subcellular resolution. We developed a mouse model of the B6 strain harbouring a bioluminescent reporter under the control of the Lysozyme M promoter. Based on the imiquimod-induced disease model of B6 mice, we used bioluminescent imaging, flow cytometry analysis, and immunohistology staining to study the effects of P140 peptides in lupus. We found a profound accumulation of CX3CR1-positive macrophages in the lungs of lupus mice after the application of P140, accompanied by lung fibrosis formation. The defined P140-mediated macrophage responses were associated with an increase of H3cit in the cytosol, interleukin-1 receptor type 1 on the extracellular membrane, and intracellular production of ROS. Of interest, the disease of imiquimod-induced lupus was prevented with an antioxidant drug apocynin. This study shows that P140 peptides play a role in aggravated murine lupus in a manner dependent on ROS production and H3cit upregulation through pulmonary macrophages.
Identifiants
pubmed: 37922035
doi: 10.1186/s43556-023-00149-9
pii: 10.1186/s43556-023-00149-9
pmc: PMC10624795
doi:
Types de publication
Journal Article
Langues
eng
Pagination
38Subventions
Organisme : Beijing Natural Science Foundation
ID : L222141
Organisme : Beijing Natural Science Foundation
ID : IS23113
Organisme : National Natural Science Foundation of China
ID : 62027901
Organisme : CAS Youth Innovation Promotion Association
ID : 2018167
Organisme : Fundamental Research Funds for the Central Universities
ID : KG16080401
Informations de copyright
© 2023. The Author(s).
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