Monocyte chemotactic protein-1-induced protein 1 contributes to neuronal injury following hypoxic-ischemia in the neonatal mouse brain
by Hailey
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Neuroinflammation has been involved in neurodegenerative diseases and acute brain injury such as stroke. monocytes chemotactic protein -1-induced protein -1 (Mcpip1) is a multifunctional protein action is known to have pro-apoptotic or anti-apoptotic depending on the nature of the experimental arrangement. However, its role in brain damage after asphyxia in the developing brain has not been studied. Therefore, we explored the role Mcpip1 on brain injury after hypoxia-ischemia in neonatal rats.
At postnatal day 7, Mcpip1-deficient and wild-type mice carotid artery ligation and exposure to hypoxia (8% oxygen). After a hypoxic-ischemic insult, we determine the time-course of cell death of apoptosis and expression levels of genes that encode proinflammatory factors. Mcpip1 impact on long-term brain damage rated one week after hypoxia-ischemia by cresyl violet staining.
We found caspase- 3 significantly increased activity in the ipsilateral brain tissue within 12-24 hours after hypoxia-ischemia. There is a marked increase in levels of mRNA transcripts that encode Mcpip1, TNF, and CCL2 in the ipsilateral brain tissue 6-48 hours after hypoxia-ischemia. We found caspase- hypoxia-ischemia-induced 3 and the activity levels of proinflammatory genes are inactivated in Mcpip1-KO mice compared to wild-type mice.
Histological assessment revealed that hypoxia-ischemia-induced brain tissue loss was significantly attenuated in the hippocampus of Mcpip1-KO mice compared to wild-type mice (9.0 ± 5.6% vs 3 3 0.9 ± 11.0%, P <0.05). Our data show that Mcpip1 contributes to acute and delayed brain damage, in part, through the regulation of neuroinflammation after hypoxic-ischemic insult in the developing rat brain.
Monocyte chemotactic protein-1-induced protein 1 contributes to neuronal injury following hypoxic-ischemia in the neonatal mouse brain
MCP-1 priming Enhanced Mesenchymal stromal cells Therapeutic Effect on Contact Hypersensitivity by Enabling COX2-PGE2 / STAT3 Pathway mesenchymal stromal
cells (MSC) has become a promising treatment for inflammation-related diseases, and the efficacy of their therapy mainly depends on the crosstalk between the MSC and inflammation. However, methods to improve the efficiency of immunosuppressive of MSC in different diseases still need to be developed. In this study, we investigated whether preconditioning MSC inflammatory cytokines associated with the disease can improve their immunosuppressive properties and increasing the success of therapy.
In a mouse model of contact hypersensitivity (CHS), an inflammatory profile screening revealed that among all the cytokines tested, monocytes chemotactic protein -1 (MCP- 1) exhibited the lowest level increased significantly in the local microenvironment. As expected, MSC asphalt with MCP-1 (P-MSCs) exhibited an enhanced ability to downregulate the secretion of proinflammatory cytokines, induce regulatory T cells, inhibiting T cell proliferation, and the polarization of M2-type macrophages.
In vivo experiments showed that P-MSCs alleviated ear swelling and local production of proinflammatory cytokines is more effective than MSC controls. Mechanically, MCP-1 can significantly activate signal transducer and activator of transcription 3 (STAT 3 ) signaling pathway and induces the expression of cyclooxygenase-2 (COX2) and prostaglandin E2 (PGE2) in the MSC. STAT 3 inhibitor reversed MCP-1-mediated increase their immunosuppressive capabilities.
Collectively, our findings indicate that MCP-1 related CHS conditioning increases immunomodulatory effects of MSC and enhanced their therapeutic efficacy in CHS. Improving the effectiveness of immunosuppressive MSC by preconditioning inflammatory cytokines associated with a particular disease may provide new strategies for MSC-based therapy for inflammatory disease.
