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Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
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Inflammatory response of endothelial cells to a human endogenous retrovirus associated with multiple sclerosis is

Alain Duperray1, Delphin Barbe1, Gilda Raguenez2

  • 1INSERM U823, F-38000 Grenoble, France Université Grenoble Alpes, IAB, F-38000 Grenoble, France.

International Immunology
|May 10, 2015
PubMed

Insights

Multiple sclerosis-associated retrovirus (MSRV) envelope protein triggers inflammation and immune cell migration across the blood-brain barrier, potentially driving multiple sclerosis (MS) pathogenesis. This retroviral protein may also contribute to other chronic inflammatory diseases.

Area of Science:

  • Neuroimmunology
  • Virology
  • Cell Biology

Background:

  • Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease affecting the central nervous system.
  • Human endogenous retroviruses (HERVs), including MSRV (multiple sclerosis-associated retrovirus), are implicated in MS pathogenesis.
  • The MSRV envelope protein (Env-ms) exhibits pro-inflammatory properties and is found in MS patients.

Purpose of the Study:

  • To investigate the molecular and functional effects of the MSRV Env-ms protein on the blood-brain barrier (BBB).
  • To elucidate the role of Env-ms in immune cell interactions with brain endothelial cells.

Main Methods:

  • Utilized an in vitro human BBB model (HCMEC/D3 brain endothelial cells).
  • Assessed Env-ms effects on inflammatory parameters, including ICAM-1, IL-6, and IL-8 expression.
  • Employed siRNA to investigate Env-ms recognition via Toll-like receptor 4 (TLR4).
  • Performed functional assays to measure immune cell adhesion and transmigration.

Main Results:

  • Env-ms induced dose-dependent overexpression of ICAM-1 and production of IL-6 and IL-8 in brain endothelial cells.
  • Env-ms recognition was mediated by TLR4 on endothelial cells.
  • Env-ms significantly enhanced the adhesion and transmigration of activated immune cells across the endothelial monolayer.
  • These findings demonstrate Env-ms disrupts BBB integrity and promotes neuroinflammation.

Conclusions:

  • The MSRV Env-ms protein plays a significant role in modulating blood-brain barrier function and promoting neuroinflammation.
  • Env-ms may contribute to the pathogenesis and maintenance of inflammatory conditions in multiple sclerosis.
  • MSRV warrants further investigation for its potential role in other chronic inflammatory diseases.
Keywords:
auto-immune diseaseblood–brain barrierleukocyte adhesionretroviral envelope

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