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LPS-induced IL-6, IL-8, VCAM-1, and ICAM-1 Expression in Human Lymphatic Endothelium

Yoshihiko Sawa, Takeshi Ueki, Minoru Hata, Kana Iwasawa, Eichi Tsuruga, Hiroshi Kojima, Hiroyuki Ishikawa and Shigemitsu Yoshida

Department of Morphological Biology (YS,ET) and Department of Oral Growth & Development (TU,MH,KI,HK,HI), Fukuoka Dental College, Fukuoka, Japan, and Department of Oral Functional Science, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan (SY)

Correspondence to: Yoshihiko Sawa, Department of Morphological Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-Ku, Fukuoka, 814-0193, Japan. E-mail: ysawa{at}college.fdc.net.ac.jp

We have previously reported the TLR4 expression in human intestinal lymphatic vessels. In the study here, microarray analysis showed the expression of the TLR4, MD-2, CD14, MyD88, TIRAP, TRAM, IRAK1, and TRAF6 genes in cultured human neonatal dermal lymphatic microvascular endothelial cells (LEC). The microarray analysis also showed that LEC expressed genes of IL-6, IL-8, VCAM-1, and ICAM-1, and the real-time quantitative PCR analysis showed that mRNA production was increased by lipopolysaccharide (LPS). The LPS-induced IL-6, IL-8, VCAM-1, and ICAM-1 production in LEC was suppressed by the introduction of TLR4-specific small interfering RNA, and also by anti-TLR4, nobiletin, and CAPE pretreatment. These findings suggest that LEC has TLR4-mediated LPS recognition mechanisms that involve at least activation of NF-B, resulting in increased expression of IL-6, IL-8, VCAM-1, and ICAM-1. Both the LPS effect on the gene expression and also the suppression by nobiletin and CAPE pretreatment on the protein production were larger in IL-6 and in VCAM-1 than in IL-8 and in ICAM-1 in LEC. The signal transduction of NF-B and AP-1-dependent pathway may be more critical for the expression of IL-6 and VCAM-1 than that of IL-8 and ICAM-1 in LEC. (J Histochem Cytochem 56:97–109, 2008)

Key Words: lymphatic endothelium • lipopolysaccharide • IL-6 • IL-8 • VCAM-1 • ICAM-1

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