title: Autonomous cure of damaged human intestinal epithelial cells by TLR2 and TLR4-dependent production of IL-22 in response to Spirulina polysaccharides.
abstract: In order to analyze the damage of human epithelial cells, we used human quasi-normal FPCK-1-1 cells derived from a colonic polyp in a patient with familial adenomatous polyposis as a monolayer, which is co-cultured with peptidoglycan (PGN)-stimulated THP-1 cells. Co-cultured FPCK-1-1 cells showed a decreased transepithelial electrical resistance (TER) and the lower level of claudin-2. When Spirulina complex polysaccharides were added one day before the start of the co-culture, there was no decrease of TER and claudin-2 (early phase damage). In contrast, when Spirulina complex polysaccharides were added to FPCK-1-1 cells after the level of TER had decreased, there was no recovery at the level of claudin-2, though the TER level recovered (late phase damage). The mucosa reconstitution is suggested to be involved in the recovery from the damaged status. Interestingly, autonomous recovery of FPCK-1-1 cells from both the early and late phase damage requires the production of IL-22, because anti-IL-22 antibodies inhibited recovery in these cases. Antibodies against either TLR2 or TLR4 inhibited the production of IL-22 from FPCK-1-1 colon epithelial cells, suggesting that signals through TLR2 and TLR4 are necessary for autonomous recovery of FPCK-1-1 colon epithelial cells by producing IL-22. In conclusion, we have established a useful model for the study of intestinal damage and recovery using human colon epithelial cells and our data suggest that damage to human colon epithelial cells can, at least in part, be recovered by the autonomous production of IL-22 in response to Spirulina complex polysaccharides.
authors.affiliation: Laboratory of Human Health and Medical Science, Graduate School of Kuroshio Science, Kochi University, Kohasu, Okoh-cho, Nankoku, Kochi 783-8505, Japan; Department of Molecular and Cellular Biology, Kochi Medical School, Kochi University, Kohasu, Okoh-cho, Nankoku, Kochi 783-8505, Japan. Electronic address: tominaga@kochi-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Tominaga
authors.forename: Yuko
authors.initials: Y
authors.lastname: Konishi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Taguchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuoka
authors.forename: Tokuichi
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Noda
authors.forename: Keiji
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D018938:Caco-2 Cells; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D062446:Claudin-2 / Q000378:metabolism; D003106:Colon / Q000166:cytology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology*; D053545:Spirulina; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014945:Wound Healing; D000097043:Interleukin-22
chemical_list: D062446:Claudin-2; D007378:Interleukins; D011134:Polysaccharides; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22; C495342:TLR2 protein, human; C495345:TLR4 protein, human
keywords: CPS; Colon epithelial cells; IL-22; LPS; PGN; PMA; PS; Spirulina complex polysaccharides; TLR2; TLR4; complex polysaccharides; lipopolysaccharides; peptidoglycan; phorbol 12-myristate 13-acetate, 12-o-tetradecanoylphorbol 13-acetate; polysaccharides