Mechanism of Regulating MK2 to Improve Bone Marrow Inflammatory Damage after Hematopoietic Stem Cell Transplantation.
10.19746/j.cnki.issn.1009-2137.2025.05.032
- Author:
Zhao-Hui WANG
1
;
Bo LONG
1
;
Yu-Han WANG
2
;
Zhi-Ting LIU
1
;
Zi-Jie XU
1
;
Shuang DING
3
Author Information
1. School of Medical Technology, Xuzhou Medical University,The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China.
2. Xuzhou Center for Disease Control and Prevention, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China.
3. Department of Clinical Laboratory Examination, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China.
- Publication Type:Journal Article
- Keywords:
allogeneic hematopoietic stem cell transplantation;
inflammation;
MK2;
NLRP3
- MeSH:
Animals;
Interleukin-1beta/metabolism*;
Rats;
Interleukin-18/metabolism*;
Hematopoietic Stem Cell Transplantation/adverse effects*;
Mice;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*;
Inflammation;
Bone Marrow/pathology*;
Protein Serine-Threonine Kinases/metabolism*;
Intracellular Signaling Peptides and Proteins/antagonists & inhibitors*;
Caspase 1/metabolism*;
Macrophages;
Transplantation, Homologous
- From:
Journal of Experimental Hematology
2025;33(5):1453-1460
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the role of MK2 inhibitor MMI-0100 on inflammatory response after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and related mechanisms.
METHODS:An allo-HSCT mouse model was established. Recipient rats were randomly divided into BMT+NaCl group and BMT+MMI-0100 group, and were injected with NaCl and MMI-0100 every day after transplantation, respectively. Samples of the two groups were collected on d 7 and 14, femur paraffin sections were stained with HE, and pathological changes in the bone marrow cavity were observed under the light microscope. The gene and protein expression levels of pro-inflammatory cytokines IL-1β and IL-18 were detected by qPCR and Western blot. Macrophage typing was detected by flow cytometry. The expression levels of NLRP3 and Caspase-1 were detected by Western blot.
RESULTS:Inflammatory cell infiltration in the bone marrow cavity was significantly reduced in the BMT+MMI-0100 group. Western blot results showed that the protein expression levels of IL-1β and IL-18 in the BMT+MMI-0100 group were decreased compared to the BMT+NaCl group on day 7 and day 14 (all P <0.01). The qPCR results showed that compared to the BMT+NaCl group, the IL-18 gene expression levels in the BMT+MMI-0100 group were significantly reduced on day 7 and day 14 (both P <0.01). In the BMT+MMI-0100 group, the expression level of IL-1β gene decreased on day 7 (P <0.05), but increased and was higher than that in the BMT+NaCl group on day 14 (P <0.05). Flow cytometry results showed that the expression of M1 macrophages and M1/M2 ratio decreased in the BMT+MMI-0100 group compared to BMT+NaCl group (all P <0.05). Western blot results showed that the protein expression levels of NLRP3 and Caspase-1 in the BMT+MMI-0100 group were lower than those in the BMT+NaCl group (all P <0.05).
CONCLUSION:MMI-0100 can ameliorate bone marrow inflammatory injury after allo-HSCT and may act by reducing NLRP3 expression to promote M2 polarization.
