uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Experimental Autoimmune Encephalomyelitis Potentiates Mouse Mast Cell Protease 4-Dependent Pressor Responses to Centrally or Systemically Administered Big Endothelin-1
Univ Sherbrooke, Med Sch, Dept Pharmacol & Physiol, Sherbrooke, PQ, Canada.
Univ Sherbrooke, Med Sch, Dept Pharmacol & Physiol, Sherbrooke, PQ, Canada.
Univ Sherbrooke, Med Sch, Dept Pharmacol & Physiol, Sherbrooke, PQ, Canada.
Univ Sherbrooke, Med Sch, Dept Pharmacol & Physiol, Sherbrooke, PQ, Canada.
Show others and affiliations
2019 (English)In: Journal of Pharmacology and Experimental Therapeutics, ISSN 0022-3565, E-ISSN 1521-0103, Vol. 370, no 3, p. 437-446Article in journal (Refereed) Published
Abstract [en]

Multiple sclerosis is a neurodegenerative disease affecting predominantly female patients between 20 and 45 years of age. We previously reported the significant contribution of mouse mast cell protease 4 (mMCP-4) in the synthesis of endothelin-1 (ET-1) in healthy mice and in a murine model of experimental autoimmune encephalomyelitis (EAE). In the current study, the cardiovascular effects of ET-1 and big endothelin-1 (big-ET-1) administered systemically or intrathecally were assessed in the early preclinical phase of EAE in telemetry instrumented/conscious mice. Chymase-specific enzymatic activity was also measured in the lung, brain, and mast cell extracts in vitro. Finally, the impact of EAE immunization was studied on the pulmonary and brain mRNA expression of different genes of the endothelin pathway, interleukin-33 (IL-33), and monitoring of immunoreactive tumor necrosis factor-α (TNF-α). Systemically or intrathecally administered big-ET-1 triggered increases in blood pressure in conscious mice. One week post-EAE, the pressor responses to big-ET-1 were potentiated in wild-type (WT) mice but not in mMCP-4 knockout (KO) mice. EAE triggered mMCP-4–specific activity in cerebral homogenates and peritoneal mast cells. Enhanced pulmonary, but not cerebral preproendothelin-1 and IL-33 mRNA were found in KO mice and further increased 1 week post-EAE immunization, but not in WT animals. Finally, TNF-α levels were also increased in serum from mMCP-4 KO mice, but not WT, 1 week post-EAE. Our study suggests that mMCP-4 activity is enhanced both centrally and systemically in a mouse model of EAE.

Place, publisher, year, edition, pages
2019. Vol. 370, no 3, p. 437-446
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-394969DOI: 10.1124/jpet.118.256016ISI: 000485873600011PubMedID: 31248979OAI: oai:DiVA.org:uu-394969DiVA, id: diva2:1360165
Available from: 2019-10-11 Created: 2019-10-11 Last updated: 2019-10-11Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Pejler, Gunnar

Search in DiVA

By author/editor
Pejler, Gunnar
By organisation
Department of Medical Biochemistry and Microbiology
In the same journal
Journal of Pharmacology and Experimental Therapeutics
Immunology in the medical area

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 4 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf