2012年4月12日 救急・ICU Journal Clubの1つの討議内容 杤久保順平先生担当
Xiahui Tan, Najwa Khalil, Candice Tesarik, Karunasri Vanapalli, Viki Yaputra, Hatem Alkhouri, Brian G. G. Oliver, Carol L. Armour, and J. Margaret Hughes
Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases
Am J Physiol Lung Cell Mol Physiol April 1, 2012 302:L700-L710; published ahead of print January 20, 2012
In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4–8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan-4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma.
さらにこれを評価しておくこと
Role of vessel wall and bone marrow syndecan-4 in neointimal hyperplasia: the plot thickens.
Caplice NM.
Arterioscler Thromb Vasc Biol. 2011 May;31(5):952-3.
CXCR7 and syndecan-4 are potential receptors for CXCL12 in human cytotrophoblasts.
Schanz A, Baston-Bust D, Krussel JS, Heiss C, Janni W, Hess AP.
J Reprod Immunol. 2011 Apr;89(1):18-25.
Synectin/syndecan-4 regulate coronary arteriolar growth during development.
Dedkov EI, Thomas MT, Sonka M, Yang F, Chittenden TW, Rhodes JM, Simons M, Ritman EL, Tomanek RJ.
Dev Dyn. 2007 Jul;236(7):2004-10.
Mechanical strain regulates syndecan-4 expression and shedding in smooth muscle cells through differential activation of MAP kinase signaling pathways.
Julien MA, Wang P, Haller CA, Wen J, Chaikof EL.
Am J Physiol Cell Physiol. 2007 Jan;292(1):C517-25.
Effects of L-arginine on fibroblast growth factor 2-induced angiogenesis in a model of endothelial dysfunction.
Voisine P, Li J, Bianchi C, Khan TA, Ruel M, Xu SH, Feng J, Rosinberg A, Malik T, Nakai Y, Sellke FW.
Circulation. 2005 Aug 30;112(9 Suppl):I202-7.
Beta1 and beta3 integrins cooperate to induce syndecan-4-containing cross-linked actin networks in human trabecular meshwork cells.
Filla MS, Woods A, Kaufman PL, Peters DM.
Invest Ophthalmol Vis Sci. 2006 May;47(5):1956-67.
Xiahui Tan, Najwa Khalil, Candice Tesarik, Karunasri Vanapalli, Viki Yaputra, Hatem Alkhouri, Brian G. G. Oliver, Carol L. Armour, and J. Margaret Hughes
Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases
Am J Physiol Lung Cell Mol Physiol April 1, 2012 302:L700-L710; published ahead of print January 20, 2012
In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4–8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan-4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma.
さらにこれを評価しておくこと
Role of vessel wall and bone marrow syndecan-4 in neointimal hyperplasia: the plot thickens.
Caplice NM.
Arterioscler Thromb Vasc Biol. 2011 May;31(5):952-3.
CXCR7 and syndecan-4 are potential receptors for CXCL12 in human cytotrophoblasts.
Schanz A, Baston-Bust D, Krussel JS, Heiss C, Janni W, Hess AP.
J Reprod Immunol. 2011 Apr;89(1):18-25.
Synectin/syndecan-4 regulate coronary arteriolar growth during development.
Dedkov EI, Thomas MT, Sonka M, Yang F, Chittenden TW, Rhodes JM, Simons M, Ritman EL, Tomanek RJ.
Dev Dyn. 2007 Jul;236(7):2004-10.
Mechanical strain regulates syndecan-4 expression and shedding in smooth muscle cells through differential activation of MAP kinase signaling pathways.
Julien MA, Wang P, Haller CA, Wen J, Chaikof EL.
Am J Physiol Cell Physiol. 2007 Jan;292(1):C517-25.
Effects of L-arginine on fibroblast growth factor 2-induced angiogenesis in a model of endothelial dysfunction.
Voisine P, Li J, Bianchi C, Khan TA, Ruel M, Xu SH, Feng J, Rosinberg A, Malik T, Nakai Y, Sellke FW.
Circulation. 2005 Aug 30;112(9 Suppl):I202-7.
Beta1 and beta3 integrins cooperate to induce syndecan-4-containing cross-linked actin networks in human trabecular meshwork cells.
Filla MS, Woods A, Kaufman PL, Peters DM.
Invest Ophthalmol Vis Sci. 2006 May;47(5):1956-67.
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