Low molecular weight lignin suppresses activation of NF-kappaB and HIV-1 promoter.
Human immunodeficiency virus type 1 (HIV-1) is a cytopathic retrovirus and the primary etiological agent of acquired immunodeficiency syndrome (AIDS) and related disorders. In cells chronically infected with HIV-1, nuclear factor-kappaB (NF-kappaB) activation by external stimuli such as tumor necrosis factor alpha (TNFalpha) augments replication of HIV-1. NF-kappaB involves in many diseases such as inflammation, cancer, and Crohn's disease. In this paper, we exhibit that (i) HIV-1gene expression was inhibited by lignin, (ii) fraction of small molecular mass in HBS lignin (less than 0.5kDa) had stronger inhibitory effects than large molecular mass (more than 1.3kDa), (iii) lignin also inhibited activation of NF-kappaB induced by TNFalpha, (iv) among six lignin dimer-like compounds, compound 6 containing beta-5 bond has more potent inhibitory activity than compounds 1, 2, 3, 4 and 5, which contain beta-1, beta-O-4, 5-5, or beta-beta structural units. These results suggested that small molecules of lignin inhibit HIV-1 replication through suppression of HIV-1 transcription from LTR including activation via NF-kappaB. Low molecular lignin may be a beneficial material or drug leads as a new class for AIDS and NF-kappaB-related diseases.
Mitsuhashi
Shinya
S
Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University, Sapporo 060-8589, Japan.
Kishimoto
Takao
T
Uraki
Yasumitsu
Y
Okamoto
Takashi
T
Ubukata
Makoto
M
D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D008031:Lignin / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D008970:Molecular Weight; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*
D016328:NF-kappa B; D008031:Lignin