Benvitimod attenuates atopic dermatitis by regulating the NRF2/ROS/NLRP3 signaling pathway
10.19405/j.cnki.issn1000-1492.2025.08.019
- VernacularTitle:PU. 1 抑制剂对 MRL/lpr 小鼠免疫功能的作用
- Author:
Tingting Guo
1
;
Nuo Xu
1
;
Kang Wang
1
;
Ying Li
1
;
Wei Wei
1
;
Shangxue Yan
2
Author Information
1. Institute of Clinical Pharmacology, Key Laboratory of Anti⁃inflammatory and Immune Medicine , Ministry of Education , Anhui Collaborative Innovation Center of Anti⁃inflammatory and Immuno Drugs , Anhui Medical University, Hefei 230032
2. Institute of Clinical Pharmacology, Key Laboratory of Anti⁃inflammatory and Immune Medicine , Ministry of Education , Anhui Collaborative Innovation Center of Anti⁃inflammatory and Immuno Drugs , Anhui Medical University, Hefei 230032 ;Experimental Animal Center, Anhui Medical University, Hefei 230032
- Publication Type:Journal Article
- Keywords:
benvitimod;
atopic dermatitis;
pyroptosis;
NLRP3;
NRF2;
ROS
- From:
Acta Universitatis Medicinalis Anhui
2025;60(8):1498-1505
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To explore the impacts and fundamental mechanisms of the PU. 1 inhibitor DB2313 on the immune function in MRL/lpr mice.
Methods:A total of thirty MRL/lpr lupus mice were randomly distributed into three separate groups : the model control group , the PU. 1 inhibitor DB2313 treatment group ( administered at a dose of 17 mg/kg) , and the positive drug control Telitacicept (TACI_Ig) group (administered at a dose of 7. 5 mg/ kg) . Furthermore , a group of ten BALB/c mice were assigned as the normal group. The DB2313 administration group was treated with intraperitoneal injections of the drug on three occasions per week , while the TACI_Ig group received subcutaneous injections every second day; both treatment protocols were maintained for a duration of five weeks. Both the control group and the model group were administered intraperitoneal injections of a volume of saline that was equivalent across groups. After the drug was given , mice were sacrificed by dislocation after orbital vein blood collection. The thymus and spleen were aseptically excised , individually weighed , and subsequently utilized to compute the thymus index and spleen index. The relative distribution of T lymphocyte subsets within the spleen was ascertained through flow cytometry. Serum concentrations of anti_nuclear antibodies ( ANA) and antidouble_stranded DNA antibodies were quantified using an enzyme_linked immunosorbent assay (ELISA) . The levels of inflammatory factors interleukin_6 (IL_6) , tumor necrosis factor_α (TNF_α) , interferon_γ(IFN_γ) were meas ured by CBA method. Hematoxylin and eosin ( HE) staining was employed to examine pathological alterations in the spleen. The expression of PU. 1 and IL_9 in spleen tissue was detected using immunohistochemistry. Additionally , the expression level of PU. 1 protein in the spleen tissue was ascertained through Western blot analysis.
Results:The administration of DB2313 significantly ameliorated spleen lesions in MRL/lpr mice and decreased the levels of anti_ds_DNA , ANA , TNF_α , IL_6 , and IFN_γ . It also reduced the proportion of total T cells , TFH cells , Th17 cells , and Th9 cells in the mouse spleen , while increasing the proportion of Treg cells. Furthermore , it lowered the level of PU. 1 protein in the spleen. Immunohistochemistry results demonstrated that DB2313 treatment significantly diminished the expression of PU. 1 and IL_9 in spleen tissue.
Conclusion:The PU. 1 inhibitor DB2313 can improve spleen lesions in MRL/lpr mice and slow the progression of the disease , and its mechanism is related to the regulation of immune cell functions.
- Full text:2026041112134602552PU.1抑制剂对MRL_lpr小鼠免疫功能的作用_郭婷婷.pdf
