Interleukin-2 receptor beta subunit-dependent and -independent regulation of intestinal epithelial tight junctions.
Interleukin (IL)-15 is able to regulate tight junction formation in intestinal epithelial cells. However, the mechanisms that regulate the intestinal barrier function in response to IL-15 and the involved subunits of the IL-15 ligand-receptor system are unknown. We determined the IL-2Rbeta subunit and IL-15-dependent regulation of tight junction-associated proteins in the human intestinal epithelial cell line T-84. The IL-2Rbeta subunit was expressed and induced signal transduction in caveolin enriched rafts in intestinal epithelial cells. IL-15-mediated tightening of intestinal epithelial monolayers correlated with the enhanced recruitment of tight junction proteins into Triton X-100-insoluble protein fractions. IL-15-mediated up-regulation of ZO-1 and ZO-2 expression was independent of the IL-2Rbeta subunit, whereas the phosphorylation of occludin and enhanced membrane association of claudin-1 and claudin-2 by IL-15 required the presence of the IL-2Rbeta subunit. Recruitment of claudins and hyperphosphorylated occludin into tight junctions resulted in a more marked induction of tight junction formation in intestinal epithelial cells than the up-regulation of ZO-1 and ZO-2 by itself. The regulation of the intestinal epithelial barrier function by IL-15 involves IL-2Rbeta-dependent and -independent signaling pathways leading to the recruitment of claudins, hyperphosphorylated occludin, ZO-1, and ZO-2 into the tight junctional protein complex.
Nishiyama
R
R
Gastrointestinal Unit, Department of Medicine, Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts 02114, USA.
Sakaguchi
T
T
Kinugasa
T
T
Gu
X
X
MacDermott
R P
RP
Podolsky
D K
DK
Reinecker
H C
HC
D001483:Base Sequence; D051242:Caveolin 1; D022461:Caveolins / Q000502:physiology; D017931:DNA Primers; D006801:Humans; D019409:Interleukin-15 / Q000502:physiology; D007413:Intestinal Mucosa / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D010766:Phosphorylation; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D015398:Signal Transduction; D019108:Tight Junctions / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D017931:DNA Primers; D019409:Interleukin-15; D008565:Membrane Proteins; D010750:Phosphoproteins; D015375:Receptors, Interleukin-2; C569042:TJP1 protein, human; C569046:TJP2 protein, human; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein