title: Fluoxetine inhibits hyperresponsive lamina propria mononuclear cells and bone marrow-derived dendritic cells, and ameliorates chronic colitis in IL-10-deficient mice.
abstract: OBJECTIVE
  We aimed to study the effect of fluoxetine on chronic colitis and its anti-inflammatory mechanism in interleukin-10-deficient (IL-10(-/-)) mice.
  
  
  METHODS
  IL-10(-/-) mice were administered with either the vehicle or one of the two dosages of fluoxetine (1 or 5 mg/kg) by oral gavage daily for 2 weeks. Lamina propria mononuclear cells (LPMCs) were isolated from IL-10(-/-) mice treated with or without fluoxetine, and cytokine expression was measured. Bone marrow-derived dendritic cells (BMDCs) isolated from IL-10(-/-), and wild-type mice were pretreated with fluoxetine and then stimulated with lipopolysaccharide. IL-12p40 and tumor necrosis factor (TNF)-α gene expression was determined by real-time PCR. DNA-binding activity of nuclear factor-κB (NF-κB) was evaluated by electrophoretic mobility shift assay.
  
  
  RESULTS
  Fluoxetine significantly reduced intestinal inflammation as assessed by body weight, colon length, and histopathological grading, and it inhibited the level of TNF-α gene expression in IL-10(-/-) mice. LPMCs were isolated from IL-10(-/-) mice, and cellular expression of IL-12p40 and interferon-γ was suppressed by fluoxetine treatment. Fluoxetine significantly inhibited IL-12p40 and TNF-α gene expression and protein secretion in BMDCs from IL-10(-/-) mice. DNA-binding activity of NF-κB was suppressed by fluoxetine pretreatment.
  
  
  CONCLUSIONS
  These results indicate that fluoxetine ameliorates intestinal inflammation in IL-10(-/-) mice and inhibits hyperresponsive LPMCs and BMDCs, which suggests that fluoxetine could be a potential therapeutic agent for inflammatory bowel disease.
authors.affiliation: Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul National University College of Medicine, 5 Gil 20, Boramae-Road, Dongjak-Gu, Seoul, 156-707, South Korea, jel1206@naver.com.
authors.forename: Seong-Joon
authors.initials: SJ
authors.lastname: Koh
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Byeong Gwan
authors.initials: BG
authors.lastname: Kim
authors.forename: Kook Lae
authors.initials: KL
authors.lastname: Lee
authors.forename: Jong Pil
authors.initials: JP
authors.lastname: Im
authors.forename: Joo Sung
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D005473:Fluoxetine / Q000494:pharmacology* / Q000627:therapeutic use; D016753:Interleukin-10 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D005473:Fluoxetine; D016753:Interleukin-10