Chloroquine, an anti-malarial agent, acts as a novel regulator of beta 1-integrin-mediated cell-cell adhesion.
Chloroquine is one of the disease-modifying antirheumatic drugs (DMARDs) with anti-malarial effect. In this study, we examined the modulatory effect of chloroquine on the functional activation of beta1-integrins (CD29) using CD29- and CD98 (a functional regulator of CD29)-mediated U937 cell-cell adhesion, comparing macrophage functions and T cell proliferation. Chloroquine effectively suppressed U937 cell-cell adhesion mediated by CD29 and CD98, in a protein kinase (PK) C, PKA, protein tyrosine kinase (PTK), extracellular signal-regulated kinase (ERK) and actin cytoskeleton-independent manner. Other lysomotropic agents (monesin, methylamine and ammonium chloride) also significantly diminished both CD29- and CD98-mediated cell-cell adhesion, indicating that lysomotropic character may play a critical role in regulating beta1-integrin functions. Therefore, these results suggest that chloroquine may act as a novel regulator of CD29 function in a lysomotropic character-dependent novel manner.
Cho
Jae Youl
JY
School of Bioscience and Biotechnology, and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Korea. jaecho@kangwon.ac.kr
D000962:Antimalarials / Q000494:pharmacology*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D027261:Fusion Regulatory Protein-1 / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism / Q000502:physiology*; D018613:Microscopy, Confocal; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020298:U937 Cells
D000962:Antimalarials; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D027261:Fusion Regulatory Protein-1; D019012:Integrin beta1; D002738:Chloroquine; D011505:Protein-Tyrosine Kinases