title: Curcumin prevents leptin-induced tight junction dysfunction in intestinal Caco-2 BBe cells.
abstract: Maintaining tight junction (TJ) integrity in the intestine is critical for nutrient absorption, host defense, and host immunity. While leptin secreted from adipose tissue is associated with obesity and obesity-related intestinal inflammation, the role of luminal leptin in intestinal TJ function is elusive. Here, we examined the role of leptin in intestinal TJ function in Caco-2 BBe cells and further explored the function of curcumin (CCM) in leptin-induced TJ dysfunction. Apical leptin, but not basolateral leptin, treatment at a concentration of 100 ng/ml deteriorated TJ function in Caco-2 BBe cells. Leptin-impaired TJ alteration was resulted from induction of leptin receptor-dependent JAK2/STAT3 signaling pathway and its-related PI3K/Akt/ERK1/2 signaling pathways. Apical leptin also lowered the expression levels of genes encoding TJ-associated proteins such as zonula occludens-3, claudin-5, and occludin, and elevated expression of pro-inflammatory genes such as IL-6 and TNF-α. Leptin-impaired TJ junction in Caco-2 BBe cells was blunted by a 30-min CCM pretreatment through inhibition of leptin receptor-dependent signaling pathway, and its-associated induction of expression of genes encoding TJ-associated proteins and pro-inflammatory cytokines. Our results elucidate a novel function of luminal leptin in intestinal TJ dysfunction, and further identify CCM as an effective dietary compound that prevents leptin-impaired TJ function in intestinal cells.
authors: Department of Food Science, Purdue University, West Lafayette, IN 47907, USA.
authors: Choon Young
authors: CY
authors: Kim
authors: Kee-Hong
authors: KH
authors: Kim
mesh_terms: D018938:Caco-2 Cells; D062507:Claudin-5 / Q000235:genetics / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D020738:Leptin / Q000009:adverse effects*; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D062825:Zonula Occludens Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C107466:CLDN5 protein, human; D062507:Claudin-5; C508600:IL6 protein, human; D015850:Interleukin-6; D020738:Leptin; C568985:OCLN protein, human; D062793:Occludin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C111873:TJP3 protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D062825:Zonula Occludens Proteins; D019869:Phosphatidylinositol 3-Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin
keywords: Caco-2 BBe; Curcumin; Leptin; Leptin signaling; Tight junction