4.7 Review

Pathophysiological and pharmacological relevance of TLR4 in peripheral immune cells after stroke

Journal

PHARMACOLOGY & THERAPEUTICS
Volume 228, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2021.107933

Keywords

TLR4; Stroke; Immune cells; Ischemic stroke; Inflammation

Funding

  1. Instituto de Salud Carlos III
  2. European Development Regional Fund A Way to Achieve Europe [PI20/00535, RETICS RD16/0019/0009]
  3. Regional Madrid Government [B2017/BMD-3688]
  4. Spanish Ministry of Science and Innovation [PID2019-106581RB-I00]
  5. Leducq Foundation for Cardiovascular Research [TNE-19CVD01]
  6. Fundacion La Caixa [HR17_00527]
  7. Instituto de Salud Carlos III (ISCIII)
  8. Ministerio de Ciencia e Innovacion (MCIN)
  9. Pro CNIC Foundation
  10. Severo Ochoa Center of Excellence [SEV-2015-0505]

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The immune response plays a crucial role in ischemic stroke, mainly by activating circulating immune cells to induce an inflammatory response. Antagonists targeting TLR4 have the potential to serve as pharmacological tools for stroke treatment.
Stroke is a very common disease being the leading cause of death and disability worldwide. The immune response subsequent to an ischemic stroke is a crucial factor in its physiopathology and outcome. This response is not limited to the injury site. In fact, the immune response to the ischemic process mobilizes mainly circulating cells which upon activation will be recruited to the injury site. When a stroke occurs, molecules that are usually retained inside the cell bodies are released into the extracellular space by uncontrolled cell death. These molecules can bind to the Toll-like receptor 4 (TLR4) in circulating immune cells which are then activated, eliciting, although not exclusively, the inflammatory response to the stroke. In this review, we present an up-to-date summary of the role of the different peripheral immune cells in stroke as well as the role of TLR4 in the function of each cell type in ischemia. Also, we summarize the different antagonists developed against TLR4 and their potential as a pharmacological tool for stroke treatment. (c) 2021 Elsevier Inc. All rights reserved.

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