title: Serotonin and melatonin, neurohormones for homeostasis, as novel inhibitors of infections by the intracellular parasite chlamydia.
abstract: OBJECTIVE
  Chlamydiae are obligate intracellular bacteria, causing a variety of diseases, i.e. pneumonia, sexually transmitted disease, conjunctivitis and zoonosis. Tryptophan depletion by interferon-gamma (IFN-gamma) is the most important host defence system against chlamydial infection. Thus chlamydial tryptophan metabolism is thought to play key roles for IFN-gamma resistance, persistent infection and host/tissue tropisms. We tested tryptophan derivatives for activity against chlamydia-infected cells.
  
  
  METHODS
  Rates of chlamydial infection and sizes of the inclusions were evaluated by in vitro infection using three Chlamydiaceae species, Chlamydia trachomatis, Chlamydophila pneumoniae and Chlamydophila felis, which show significant divergence of tryptophan synthesis genes and different susceptibilities to IFN-gamma.
  
  
  RESULTS
  Melatonin and serotonin, which are recognized as neural hormones for maintenance of organism homeostasis, reduced chlamydial infection but not other bacterial growth tested here. Unlike IFN-gamma, melatonin limited infection of all three chlamydiae and the effects were not recovered by tryptophan supplementation. Melatonin treatment only of host cells could diminish infection and the infection reduction was neutralized by a pertussis toxin, an inhibitor of G proteins. Ligands of melatonin and serotonin receptors also hampered infection.
  
  
  CONCLUSIONS
  Inhibition mechanisms of chlamydial infection by melatonin and serotonin appear to be different from those of IFN-gamma and involve specific G-protein-coupled receptors. Melatonin is deemed to inhibit early progression of the chlamydial development cycle, such as establishment of intracellular infection and/or conversion from elementary body to reticulate body. Utilization of melatonin, serotonin or their derivatives may be advantageous for harmless prevention of chlamydial infection.
authors.affiliation: Department of Microbiology, Yamaguchi University School of Medicine, 1-1-1, Minamikogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Mohd Akhlakur
authors.initials: MA
authors.lastname: Rahman
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Azuma
authors.forename: Hajime
authors.initials: H
authors.lastname: Fukunaga
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Murakami
authors.forename: Kazurou
authors.initials: K
authors.lastname: Sugi
authors.forename: Hideto
authors.initials: H
authors.lastname: Fukushi
authors.forename: Koshiro
authors.initials: K
authors.lastname: Miura
authors.forename: Harumi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Mutsunori
authors.initials: M
authors.lastname: Shirai
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002689:Chlamydia / Q000187:drug effects* / Q000254:growth & development; D002692:Chlamydia trachomatis / Q000187:drug effects / Q000254:growth & development; D016993:Chlamydophila pneumoniae / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D002479:Inclusion Bodies; D007371:Interferon-gamma / Q000494:pharmacology; D008550:Melatonin / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000633:toxicity; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D014364:Tryptophan / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D043562:Receptors, G-Protein-Coupled; D012701:Serotonin; D007371:Interferon-gamma; D014364:Tryptophan; D037342:Pertussis Toxin; D008550:Melatonin