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Dexamethasone downregulates the expressions of MMP-9 and oxidative stress in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection.
Parasitology. 2021 02; 148(2):187-197.P

Abstract

Steroids have been shown to be beneficial in patients and mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection; however, the mechanism for this beneficial effect is unknown. We speculated that the effect of steroids in eosinophilic meningitis caused by A. cantonensis infection may be mediated by the downregulation of matrix metallopeptidase-9 (MMP-9) and oxidative stress pathways via glucocorticoid receptors (GRs). We found blood-brain barrier (BBB) dysfunction in mice with eosinophilic meningitis 2-3 weeks after infection as evidenced by increased extravasation of Evans blue and cerebrospinal fluid (CSF) albumin levels. The administration of dexamethasone significantly decreased the amount of Evans blue and CSF albumin. The effect of dexamethasone was mediated by GRs and heat shock protein 70, resulting in subsequent decreases in the expressions of nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in the CSF and brain parenchymal after 2 weeks of steroid administration. Steroid treatment also decreased CSF/brain homogenate MMP-9 concentrations, but had no effect on CSF MMP-2 levels, indicating that MMP-9 rather than MMP-2 played a major role in BBB dysfunction in mice with eosinophilic meningitis. The concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) gradually increased after 1-3 weeks of infection, and the administration of dexamethasone significantly downregulated the concentration of oxidized derivative 8-OHdG in CSF. In conclusion, increased 8-OHdG and MMP-9 concentrations were found in mice with eosinophilic meningitis caused by A. cantonensis infection. The effect of dexamethasone was mediated by GRs and significantly decreased not only the levels of 8-OHdG and MMP-9 but also NF-κB, JNK and ERK.

Authors+Show Affiliations

Section of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. National Yang-Ming University, Taipei, Taiwan. Department of Parasitology and Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.Section of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. National Yang-Ming University, Taipei, Taiwan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33004090

Citation

Tsai, Hung-Chin, and Yu-Hsin Chen. "Dexamethasone Downregulates the Expressions of MMP-9 and Oxidative Stress in Mice With Eosinophilic Meningitis Caused By Angiostrongylus Cantonensis Infection." Parasitology, vol. 148, no. 2, 2021, pp. 187-197.
Tsai HC, Chen YH. Dexamethasone downregulates the expressions of MMP-9 and oxidative stress in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection. Parasitology. 2021;148(2):187-197.
Tsai, H. C., & Chen, Y. H. (2021). Dexamethasone downregulates the expressions of MMP-9 and oxidative stress in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection. Parasitology, 148(2), 187-197. https://doi.org/10.1017/S0031182020001870
Tsai HC, Chen YH. Dexamethasone Downregulates the Expressions of MMP-9 and Oxidative Stress in Mice With Eosinophilic Meningitis Caused By Angiostrongylus Cantonensis Infection. Parasitology. 2021;148(2):187-197. PubMed PMID: 33004090.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dexamethasone downregulates the expressions of MMP-9 and oxidative stress in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection. AU - Tsai,Hung-Chin, AU - Chen,Yu-Hsin, Y1 - 2020/10/02/ PY - 2020/10/3/pubmed PY - 2021/9/30/medline PY - 2020/10/2/entrez KW - Angiostrongylus cantonensis KW - corticosteroid KW - eosinophilic meningitis KW - oxidative stress SP - 187 EP - 197 JF - Parasitology JO - Parasitology VL - 148 IS - 2 N2 - Steroids have been shown to be beneficial in patients and mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection; however, the mechanism for this beneficial effect is unknown. We speculated that the effect of steroids in eosinophilic meningitis caused by A. cantonensis infection may be mediated by the downregulation of matrix metallopeptidase-9 (MMP-9) and oxidative stress pathways via glucocorticoid receptors (GRs). We found blood-brain barrier (BBB) dysfunction in mice with eosinophilic meningitis 2-3 weeks after infection as evidenced by increased extravasation of Evans blue and cerebrospinal fluid (CSF) albumin levels. The administration of dexamethasone significantly decreased the amount of Evans blue and CSF albumin. The effect of dexamethasone was mediated by GRs and heat shock protein 70, resulting in subsequent decreases in the expressions of nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in the CSF and brain parenchymal after 2 weeks of steroid administration. Steroid treatment also decreased CSF/brain homogenate MMP-9 concentrations, but had no effect on CSF MMP-2 levels, indicating that MMP-9 rather than MMP-2 played a major role in BBB dysfunction in mice with eosinophilic meningitis. The concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) gradually increased after 1-3 weeks of infection, and the administration of dexamethasone significantly downregulated the concentration of oxidized derivative 8-OHdG in CSF. In conclusion, increased 8-OHdG and MMP-9 concentrations were found in mice with eosinophilic meningitis caused by A. cantonensis infection. The effect of dexamethasone was mediated by GRs and significantly decreased not only the levels of 8-OHdG and MMP-9 but also NF-κB, JNK and ERK. SN - 1469-8161 UR - https://www.unboundmedicine.com/medline/citation/33004090/Dexamethasone_downregulates_the_expressions_of_MMP_9_and_oxidative_stress_in_mice_with_eosinophilic_meningitis_caused_by_Angiostrongylus_cantonensis_infection_ L2 - https://www.cambridge.org/core/product/identifier/S0031182020001870/type/journal_article DB - PRIME DP - Unbound Medicine ER -