Eva Latorre1,2, Elena Layunta2,3, Laura Grasa2,3, Julián Pardo4, Santiago García5, Ana I Alcalde2, José E Mesonero2,3. 1. 1Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, United Kingdom. 2. Departamento Farmacología y Fisiología, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Zaragoza, Spain. 3. Instituto Agroalimentario de Aragón - IA2 - (Universidad de Zaragoza - CITA), Zaragoza, Spain. 4. Departamento Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Zaragoza, Spain. 5. Servicio de Sistema Digestivo, Hospital Clínico Universitario "Miguel Servet", Instituto de Investigación Sanitaria de Aragón (IIS) Zaragoza, Spain.
Abstract
BACKGROUND: Inflammatory bowel diseases are consequence of an intestinal homeostasis breakdown in which innate immune dysregulation is implicated. Toll-like receptor (TLR)2 and TLR4 are immune recognition receptors expressed in the intestinal epithelium, the first physical-physiological barrier for microorganisms, to inform the host of the presence of Gram-positive and Gram-negative organisms. Interleukin (IL)-10 is an essential anti-inflammatory cytokine that contributes to maintenance of intestinal homeostasis. AIM: Our main aim was to investigate intestinal IL-10 synthesis and release, and whether TLR2 and TLR4 are determinants of IL-10 expression in the intestinal tract. METHODS: We used Caco-2 cell line as an enterocyte-like cell model, and also ileum and colon from mice deficient in TLR2, TLR4 or TLR2/4 to test the involvement of TLR signaling. RESULTS: Intestinal epithelial cells are able to synthesize and release IL-10 and their expression is increased after TLR2 or TLR4 activation. IL-10 regulation seems to be tissue specific, with IL-10 expression in the ileum regulated by a compensation between TLR2 and TLR4 expression, whereas in the colon, TLR2 and TLR4 affect IL-10 expression independently. CONCLUSIONS: Intestinal epithelial cells could release IL-10 in response to TLR activation, playing an intestinal tissue-dependent and critical intestinal immune role.
BACKGROUND: Inflammatory bowel diseases are consequence of an intestinal homeostasis breakdown in which innate immune dysregulation is implicated. Toll-like receptor (TLR)2 and TLR4 are immune recognition receptors expressed in the intestinal epithelium, the first physical-physiological barrier for microorganisms, to inform the host of the presence of Gram-positive and Gram-negative organisms. Interleukin (IL)-10 is an essential anti-inflammatory cytokine that contributes to maintenance of intestinal homeostasis. AIM: Our main aim was to investigate intestinal IL-10 synthesis and release, and whether TLR2 and TLR4 are determinants of IL-10 expression in the intestinal tract. METHODS: We used Caco-2 cell line as an enterocyte-like cell model, and also ileum and colon from mice deficient in TLR2, TLR4 or TLR2/4 to test the involvement of TLR signaling. RESULTS: Intestinal epithelial cells are able to synthesize and release IL-10 and their expression is increased after TLR2 or TLR4 activation. IL-10 regulation seems to be tissue specific, with IL-10 expression in the ileum regulated by a compensation between TLR2 and TLR4 expression, whereas in the colon, TLR2 and TLR4 affect IL-10 expression independently. CONCLUSIONS: Intestinal epithelial cells could release IL-10 in response to TLR activation, playing an intestinal tissue-dependent and critical intestinal immune role.
Entities:
Keywords:
Interleukin-10; Toll-like receptors; cytokine; enterocyte; epithelium; gut
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