Lymphotoxin-{alpha}3 mediates monocyte-endothelial interaction by TNFR I/NF-{kappa}B signaling

Journal Article · Fri Feb 06 04:00:00 EST 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2008.12.064· OSTI ID:21255862

Suna, Shinichiro ^[1]; Sakata, Yasuhiko ^[1]; Shimizu, Masahiko; Nakatani, Daisaku; Usami, Masaya; Matsumoto, Sen; Mizuno, Hiroya ^[1]; Ozaki, Kouichi ^[2]; Takashima, Seiji ^[1]; Takeda, Hiroshi ^[3]; Tanaka, Toshihiro ^[2]; Hori, Masatsugu ^[4]; Sato, Hiroshi ^[1]

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1. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)
2. Laboratory for Cardiovascular Diseases, Center for Genomic Medicine, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045 (Japan)
3. Department of Medical Information Science, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)
4. Osaka Medical Center for Cancer and Cardiovascular Disease, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511 (Japan)

We recently reported that the single nucleotide polymorphisms of the lymphotoxin-(LT){alpha} gene, a member of the tumor necrosis factor (TNF) family, are closely related to acute myocardial infarction; however, the precise mechanism of LT{alpha} signaling in atherogenesis remains unclear. We investigated the role of LT{alpha}3, a secreted homotrimer of LT{alpha}, in monocyte-endothelial cell adhesion using cultured human umbilical vein endothelial cells (HUVEC). We found that LT{alpha}3 induced cell adhesion molecules and activated NF-{kappa}B p50 and p65. LT{alpha}3 also induced phosphorylation of Akt, phosphorylation and degradation of I{kappa}B, nuclear translocation of p65, and increased adhesion of THP1 monocytes to HUVEC. These effects were mediated by TNF receptor (TNFR) I and attenuated by the phosphatidylinositol triphosphate-kinase (PI3K) inhibitors LY294002 and Wortmannin. Thus, LT{alpha}3 mediates the monocyte-endothelial interaction via the classical NF-{kappa}B pathway following TNFR I/PI3K activation, indicating it may play a role in the development of coronary artery disease.

• OSTI ID: 21255862
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 379; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADHESION
ARTERIOSCLEROSIS
CORONARIES
GENES
HUMAN POPULATIONS
MONOCYTES
MYOCARDIAL INFARCTION
NUCLEOTIDES
PHOSPHORYLATION
RECEPTORS
VEINS