Korean J Parasitol.  2016 Feb;54(1):31-38. 10.3347/kjp.2016.54.1.31.

Afatinib Reduces STAT6 Signaling of Host ARPE-19 Cells Infected with Toxoplasma gondii

  • 1Department of Parasitology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea. howoo@catholic.ac.kr
  • 2Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.


Specific gene expressions of host cells by spontaneous STAT6 phosphorylation are major strategy for the survival of intracellular Toxoplasma gondii against parasiticidal events through STAT1 phosphorylation by infection provoked IFN-γ. We determined the effects of small molecules of tyrosine kinase inhibitors (TKIs) on the growth of T. gondii and on the relationship with STAT1 and STAT6 phosphorylation in ARPE-19 cells. We counted the number of T. gondii RH tachyzoites per parasitophorous vacuolar membrane (PVM) after treatment with TKIs at 12-hr intervals for 72 hr. The change of STAT6 phosphorylation was assessed via western blot and immunofluorescence assay. Among the tested TKIs, Afatinib (pan ErbB/EGFR inhibitor, 5 µM) inhibited 98.0% of the growth of T. gondii, which was comparable to pyrimethamine (5 µM) at 96.9% and followed by Erlotinib (ErbB1/EGFR inhibitor, 20 µM) at 33.8% and Sunitinib (PDGFR or c-Kit inhibitor, 10 µM) at 21.3%. In the early stage of the infection (2, 4, and 8 hr after T. gondii challenge), Afatinib inhibited the phosphorylation of STAT6 in western blot and immunofluorescence assay. Both JAK1 and JAK3, the upper hierarchical kinases of cytokine signaling, were strongly phosphorylated at 2 hr and then disappeared entirely after 4 hr. Some TKIs, especially the EGFR inhibitors, might play an important role in the inhibition of intracellular replication of T. gondii through the inhibition of the direct phosphorylation of STAT6 by T. gondii.


Toxoplasma gondii; growth inhibition; small molecule; tyrosine kinase inhibitor; EGFR; Afatinib; STAT6 phosphorylation

MeSH Terms

Antiparasitic Agents/pharmacology
Blotting, Western
Cell Line
Enzyme Activation/drug effects
Fluorescent Antibody Technique
Janus Kinase 1/metabolism
Janus Kinase 3/metabolism
Phosphorylation/drug effects
STAT6 Transcription Factor/*metabolism
Signal Transduction/*drug effects
Toxoplasma/*drug effects/physiology
Antiparasitic Agents
Janus Kinase 1
Janus Kinase 3
STAT6 Transcription Factor
Full Text Links
  • KJP
export Copy
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr