Allicin inhibits SDF-1alpha-induced T cell interactions with fibronectin and endothelial cells by down-regulating cytoskeleton rearrangement, Pyk-2 phosphorylation and VLA-4 expression.
Allicin, a major ingredient of fresh garlic extract that is produced during the crushing of garlic cloves, exerts various beneficial biological effects, including a broad spectrum of antimicrobial activity, antihyperlipidaemic and antihypertensive effects. However, how allicin affects the immune system is less well known, and its effect on human T cells has never been studied. Here, we examined the in-vitro effects of allicin on the functioning of T cells related to their entry to inflamed extravascular sites. We found that allicin (20-100 microm) inhibits the SDF-1alpha (CXCL12)-induced T cell migration through fibronectin (FN), and that this inhibition is mediated by the down-regulation of (i) the reorganization of cortical actin and the subsequent T cell polarization, and (ii) T cell adhesion to FN. Moreover, allicin also inhibited T cell adhesion to endothelial cells and transendothelial migration. The mechanisms underlying these inhibitory effects of allicin are associated with its ability to down-regulate the phosphorylation of Pyk2, an intracellular member of the focal adhesion kinases, and to reduce the expression of the VCAM-1- and FN-specific alpha4beta1-integrin (VLA-4). The ability of allicin to down-regulate these chemokine-induced and VLA-4-mediated T cell functions explains its beneficial biological effects in processes where T cells play an important role and suggests that allicin may be used therapeutically with chronic inflammatory diseases.
Sela
Uri
U
Department of Immunology, The Weizmann Institute of Science, Rehovot 76 100, Israel. uri.sela@weizmann.ac.il
Ganor
Sharon
S
Hecht
Iris
I
Brill
Alexander
A
Miron
Talia
T
Rabinkov
Aharon
A
Wilchek
Meir
M
Mirelman
David
D
Lider
Ofer
O
Hershkoviz
Rami
R
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects; D004220:Disulfides; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology; D005353:Fibronectins / Q000378:metabolism; D051418:Focal Adhesion Kinase 2; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism; D046911:Macromolecular Substances; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013441:Sulfinic Acids / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000199:Actins; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D004220:Disulfides; D005353:Fibronectins; D039041:Integrin alpha4beta1; D046911:Macromolecular Substances; D013441:Sulfinic Acids; C006452:allicin; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2