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IL‐6 INDUCES KERATIN EXPRESSION IN INTESTINAL EPITHELIAL CELLS: POTENTIAL ROLE OF KERATIN‐8 IN IL‐6 INDUCED BARRIER FUNCTION ALTERATIONS
Author(s) -
Wang Lixin,
Srinivasan Shanthi,
Merlin Didier,
Sitaraman Shanthi V
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a588-c
Subject(s) - paracellular transport , barrier function , microbiology and biotechnology , western blot , keratin , keratin 8 , chemistry , keratin 5 , intestinal mucosa , tight junction , biology , medicine , permeability (electromagnetism) , biochemistry , paleontology , membrane , gene
The regulation and function of keratin in the intestinal epithelia is largely unknown. In this study we addressed the role and regulation of K8 and K18 expression by IL‐6. Caco2‐BBE cell line and IL‐6 null mice were used to study the effect of IL‐6 on keratin expression. Keratin expression was studied by Northern blot, Western blot and confocal microscopy. Paracellular permeability was assessed by apical‐to‐basal transport of a FITC dextran probe (FD‐4). K8 was silenced using siRNA approach. IL‐6 significantly upregulated mRNA and protein levels of K8 and K18. Confocal microscopy showed a reticular pattern of intracellular keratin localized to the sub‐apical region after IL‐6 treatment. IL‐6 also induced serine phosphorylation of K8. IL‐6 decreased paracellular flux of FD‐4 compared to vehicle treated monolayer. K8 silencing abolished the decrease in paracellular permeability induced by IL‐6. Interestingly, IL‐6−/− mice showed decreased baseline levels of K8/K18 expression. Administration of dextran sodium sulfate (DSS) significantly increased intestinal permeability in IL‐6−/− mice compared to WT mice given DSS. Collectively, our data demonstrate that IL‐6 regulates the colonic expression of K8 and K18 and K8/K18 mediates barrier protection by IL‐6 under conditions where intestinal barrier is compromised. Thus our data uncover a novel function of these abundant cytoskeletal proteins which may have implications in intestinal disorders such as inflammatory bowel disease wherein barrier dysfunction underlies the inflammatory response.