Leukocyte adhesion molecule and chemokine production through lipoteichoic acid recognition by toll-like receptor 2 in cultured human lymphatic endothelium.
We have recently reported that the human lymphatic endothelium has toll-like receptor 4 (TLR4)-mediated lipopolysaccharide recognition mechanisms that induce the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Although ligand engagement with TLR2 enables activation of the MyD88-dependent pathway similarly to TLR4, whether TLR2 ligands such as lipoteichoic acid (LTA) trigger the activation of lymphatic endothelium remains unclear. This study has been designed to investigate the expression dynamics of LTA-induced leukocyte adhesion molecules and chemokines in cultured human lymphatic endothelium (LEC). Reverse transcription/polymerase chain reaction (RT-PCR) and real-time quantitative PCR analyses have shown that LEC usually expresses TLR2 and increases TLR2 gene expression on LTA treatment. Indeed, LTA-treated LEC increases the expression of E-selectin, ICAM-1, and VCAM-1 but does not alter the gene expression of ICAM-2, ICAM-3, junctional adhesion molecule-1 (JAM-1), JAM-3, or platelet endothelial cell adhesion molecule-1 (PECAM-1). The expression of LTA-induced E-selectin, ICAM-1, and VCAM-1 in LEC is suppressed by anti-TLR2 but not by anti-TLR4 and is also suppressed by TLR2-specific short interfering RNA (siRNA) but not by siRNA for TLR4. The expression of CCL2, CCL5, and CCL20 (Cys-Cys motif chemokines) and of CXCL1, CXCL3, CXCL5, CXCL6, and CXCL8 (Cys-X-Cys motif chemokines) was induced in LEC with LTA. These data suggest that the human lymphatic endothelial phenotype has TLR2-mediated LTA-recognition mechanisms, resulting in increased expression of inflammatory leukocyte adhesion molecules and phagocyte-attractive chemokines. The human lymphatic endothelium may thus function to collect leukocytes from tissues into lymphatic vessels by means of immunologically functional molecules.
Department of Morphological Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-Ku, Fukuoka, Japan. ysawa@college.fdcnet.ac.jp
Yoshihiko
Y
Sawa
Eichi
E
Tsuruga
Kana
K
Iwasawa
Hiroyuki
H
Ishikawa
Shigemitsu
S
Yoshida
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D013682:Teichoic Acids / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D015815:Cell Adhesion Molecules; D018925:Chemokines; D019040:E-Selectin; C407243:F11R protein, human; C448000:JAM3 protein, human; D008070:Lipopolysaccharides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C009900:lipoteichoic acid