Lymphotoxin inhibits Chlamydia pneumoniae growth in HEp-2 cells.
Cytokines such as gamma interferon and tumor necrosis factor alpha (TNF-alpha) inhibit the intracellular replication of Chlamydia pneumoniae or Chlamydia trachomatis. In this study, we found that another cytokine, lymphotoxin (TNF-beta), restricts the growth of C. pneumoniae in HEp-2 cells. When lymphotoxin (10 U/ml) was added during incubation from 8 to 16 h postinoculation, inclusion body formation was severely reduced. In addition, we observed activation of nitric oxide production and the nuclear transition of NF-kappaB in HEp-2 cells in response to lymphotoxin. These results suggest that inhibition of chlamydial growth by lymphotoxin is mediated, at least in part, by nuclear transition of NF-kappaB, resulting in induction of nitric oxide synthase to produce nitric oxide, a potent bacteristatic agent. This is the first report on antichlamydial activity of lymphotoxin through induction of nitric oxide.
Matsushima
H
H
Department of Microbiology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Shirai
M
M
Ouchi
K
K
Yamashita
K
K
Kakutani
T
T
Furukawa
S
S
Nakazawa
T
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016993:Chlamydophila pneumoniae / Q000187:drug effects* / Q000254:growth & development; D006224:Cricetinae; D006801:Humans; D008233:Lymphotoxin-alpha / Q000378:metabolism / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D008233:Lymphotoxin-alpha; D016328:NF-kappa B; D009569:Nitric Oxide