Imiquimod: The biochemical mechanisms of immunomodulatory and anti-inflammatory activity

  • S. V. Bozrova
  • V. A. Levitsky
  • S. A. Nedospasov
  • M. S. Drutskaya
Article

DOI: 10.1134/S1990750813020042

Cite this article as:
Bozrova, S.V., Levitsky, V.A., Nedospasov, S.A. et al. Biochem. Moscow Suppl. Ser. B (2013) 7: 136. doi:10.1134/S1990750813020042
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Abstract

Imidazoquinolines are a new group of compounds that recently have been introduced into clinical practice as antitumor and antiviral immunomodulators. Structurally, they are low molecular weight synthetic guanosine-like molecules. Although imiquimod, the most widely used imidazoquinoline, has been recommended for treatment of several forms of skin cancer and papillomas, its molecular mechanisms of action are not fully understood. In particular, imiquimod is known as a specific agonist of Toll-like receptor 7 (TLR7) and this capacity is widely used in a large number of experimental studies and clinical trials. Nevertheless, detailed analysis of the published data suggests that the biological activity of imiquimod can not be explained only by its interaction with TLR7. Certain evidence exists that imiquimod directly interacts with adenosine receptors and other molecules that regulate synthesis of cyclic adenosine monophosphate. A detailed understanding of the biochemical basis of immunomodulating and antitumor effects of imiquimod will increase its clinical effectiveness and accelerate the development of new drugs with similar but improved pharmaceutical characteristics. This review summarizes the published data about effects of imiquimod on various intracellular biochemical processes and signaling pathways.

Keywords

imidazoquinolines imiquimod tumor necrosis factor anti-inflammatory drug cAMP 

Abbreviations used

AC

adenylate cyclase

APC

antigen presenting cell

ATP

adenosine triphosphate

cAMP

cyclic adenosine monophosphate

CCPA

chloro-N6-cyclopentyladenosine

CHO

Chinese hamster ovary

COX-2

cyclooxygenase-2

CNS

central nervous system

DC

dendritic cell

fMLP

formyl-methionyl-leucyl-phenylalanine

G-CSF

granulocyte colony-stimulating factor

IFN

interferon

IL

interleukin

IP-10

interferon-gamma induced protein 10

HPV

human papillomavirus

MIIC

compartment of major histocompatibility complex class II

MCP

monocyte chemoattractant protein

MHC

major histocompatibility complex

MIP-1α, 1β

macrophage-induced protein 1α, 1β

NF-κB

nuclear factor kappa B

NK

natural killer

OGF

opioid growth factor

OGFR

receptor of opioid growth factor

PDE

phosphodiesterase

PKA

protein kinase A

Th

T-helper

TCR

T-cell receptor

TLR

Toll-like receptor

TNF

tumor necrosis factor

Copyright information

© Pleiades Publishing, Ltd. 2013

Authors and Affiliations

  • S. V. Bozrova
    • 1
    • 2
  • V. A. Levitsky
    • 1
    • 3
  • S. A. Nedospasov
    • 1
    • 2
  • M. S. Drutskaya
    • 1
    • 3
  1. 1.Engelhardt Institute of Molecular Biology RASMoscowRussia
  2. 2.Department of Immunology, Biological FacultyLomonosov Moscow State UniversityMoscowRussia
  3. 3.Oncology DepartmentJohns Hopkins University School of Medicine, Roche GlycartSchlierenSwitzerland

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