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Fluoxetine inhibits hyperresponsive lamina propria mononuclear cells and bone marrow-derived dendritic cells, and ameliorates chronic colitis in IL-10-deficient mice
- Source :
- Digestive diseases and sciences. 60(1)
- Publication Year :
- 2013
-
Abstract
- We aimed to study the effect of fluoxetine on chronic colitis and its anti-inflammatory mechanism in interleukin-10-deficient (IL-10(-/-)) mice.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.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.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.
- Subjects :
- Male
medicine.medical_specialty
Lipopolysaccharide
Physiology
Anti-Inflammatory Agents
Bone Marrow Cells
Electrophoretic Mobility Shift Assay
Peripheral blood mononuclear cell
chemistry.chemical_compound
Mice
Internal medicine
Fluoxetine
medicine
Animals
Colitis
Intestinal Mucosa
Lamina propria
Gastroenterology
NF-kappa B
Dendritic cell
Dendritic Cells
medicine.disease
Interleukin-10
Mice, Inbred C57BL
Interleukin 10
Disease Models, Animal
Endocrinology
medicine.anatomical_structure
chemistry
Chronic Disease
Leukocytes, Mononuclear
Cytokines
Tumor necrosis factor alpha
Bone marrow
Subjects
Details
- ISSN :
- 15732568
- Volume :
- 60
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Digestive diseases and sciences
- Accession number :
- edsair.doi.dedup.....3a4525fa176b8a396fb3f57301308f49