mast cell tryptase controls paracellular permeability of the intestine
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DESCRIPTIONMast Cell Tryptase Controls Paracellular Permeability of the Intestine. 生科四甲 陳子甯. 作者假設：. mast cells signal to colonocytes by release of tryptase and activation of PAR2, and that PAR2 couples to ERK1/2 by a β ARR-dependent mechanism to regulate TJs. TJ: tight junction. - PowerPoint PPT Presentation
Mast Cell Tryptase Controls Paracellular Permeabilityof the Intestine
mast cells signal to colonocytes by release of tryptase and activation of PAR2, and that PAR2 couples to ERK1/2 by a ARR-dependent mechanism to regulate TJs.
ERK1/2extracellular signal-regulated kinases 1/2ARR:-arrestinTJ: tight junction
mast cell tryptasePAR2colonocytes
ERK1/2extracellular signal-regulated kinases 1/2ARR:-arrestin
Model for -arrestin-dependent activation of ERK1/2 by PAR2
microtubule-associated proteins (MAPs) phospholipase A2 (PLA2) Ca2+
FIG. 1. Expression of mRNA encoding PAR2 and trypsinogen IV by colonocytes.
FIG. 2. PAR2-mediated mobilization of [Ca2+]i in colonocytes.
FIG. 3. PAR2-mediated mobilization of [Ca2+]i in colonocytes.
FIG. 4. Characterization of CHMC.
mast cellIgE bindingdegranuledCHMC
CHMCmast cellSBTI: Soybean trypsin inhibitormast celltryptasedegranule
FIG. 5. Mast cell signaling to colonocytes.
48/80mast cell degranule mast celldegranuletryptasesupernatant formcolonocytes
TER ( transepithelial resistance ) & paracellular permeability
FIG. 6. Effects of PAR2 agonists on paracellular permeability.
PAR2 Activation Increases Paracellular Permeability
FIG. 7. PAR2-induced redistribution of TJ proteins and F-actin detected by microscopy
PAR2TJ protein F-actin redistribution
FIG. 8. PAR2-induced redistribution of TJ proteins detected by subcellular fractionation and Western blotting.
PAR2TJ proteinsredistributionE-cadherin is a transmembrane glycoprotein that mediates epithelial cell-to-cell adhesion.
FIG. 9. Effects of mast cell products on paracellular permeability.
FIG. 10. ERK1/2-mediated changes in paracellular permeability.
ERK1/2 paracellular permeabilityPAR2ERK1/2PAR2paracellular permeabilityUO126ERK1/2
FIG. 11. Down-regulation of ARR using siRNAARR1ARR2498bp381bpARR cytoplasm-nucleus messengerPAR2ERK1/2 ARR ERK1/2
FIG. 12. ARR-mediated changes in paracellular permeability.
Oligofectamine ARR ERK1/2 bindingPAR2ARR ERK1/2colonocytes
Colonocytes expressed PAR2 mRNA and responded to PAR2 agonists with increased [Ca2+]i
Mast cells signal to colonocytes in a paracrine manner by release of tryptase and activation of PAR2.