title: Human mesenchymal stem cells suppress the stretch-induced inflammatory miR-155 and cytokines in bronchial epithelial cells.
abstract: Current research in pulmonary pathology has focused on inflammatory reactions initiated by immunological responses to allergens and irritants. In addition to these biochemical stimuli, physical forces also play an important role in regulating the structure, function, and metabolism of the lung. Hyperstretch of lung tissues can contribute to the inflammatory responses in asthma, but the mechanisms of mechanically induced inflammation in the lung remain unclear. Our results demonstrate that excessive stretch increased the secretion of inflammatory cytokines by human bronchial epithelial cells (hBECs), including IL-8. This increase of IL-8 secretion was due to an elevated microRNA-155 (miR-155) expression, which caused the suppression of Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) production and the subsequent activation of JNK signaling. In vivo studies in our asthmatic mouse model also showed such changes in miR-155, IL-8, and SHIP1 expressions that reflect inflammatory responses. Co-culture with human mesenchymal stem cells (hMSCs) reversed the stretch-induced hBEC inflammatory responses as a result of IL-10 secretion by hMSCs to down-regulate miR-155 expression in hBECs. In summary, we have demonstrated that mechanical stretch modulates the homeostasis of the hBEC secretome involving miR-155 and that hMSCs can be used as a potential therapeutic approach to reverse bronchial epithelial inflammation in asthma.
authors: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Yi-Chun
authors: YC
authors: Kuo
authors: Yi-Shuan Julie
authors: YS
authors: Li
authors: Jing
authors: J
authors: Zhou
authors: Yu-Ru Vernon
authors: YR
authors: Shih
authors: Marina
authors: M
authors: Miller
authors: David
authors: D
authors: Broide
authors: Oscar Kuang-Sheng
authors: OK
authors: Lee
authors: Shu
authors: S
authors: Chien
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism*; D002460:Cell Line; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D000072181:Inositol Polyphosphate 5-Phosphatases; D008168:Lung / Q000378:metabolism / Q000473:pathology; D055595:Mechanical Phenomena; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010047:Ovalbumin / Q000009:adverse effects; D019899:Paracrine Communication; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D010047:Ovalbumin; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606430:INPP5D protein, human; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
references: Am Rev Respir Dis. 1987 Mar;135(3):591-6
references: 3826885
references: J Cell Sci. 2011 Nov 1;124(Pt 21):3581-90
references: 22045729
references: Stem Cells. 2007 Apr;25(4):903-10
references: 17218399
references: BMC Genomics. 2007 Jul 17;8:240
references: 17640343
references: Thorax. 2012 Jun;67(6):496-501
references: 22106021
references: Hepatology. 2004 Dec;40(6):1275-84
references: 15562440
references: Respir Physiol. 1973 Jan;17(1):113-26
references: 4688282
references: Int Rev Immunol. 2009;28(5):264-84
references: 19811312
references: Gene Ther. 2003 Apr;10(8):621-9
references: 12692590
references: Curr Drug Targets. 2008 Jun;9(6):485-94
references: 18537587
references: Am Rev Respir Dis. 1980 Feb;121(2):297-305
references: 7362137
references: Am J Physiol Lung Cell Mol Physiol. 2002 May;282(5):L892-6
references: 11943651
references: Diabetes. 2008 Jul;57(7):1759-67
references: 18586907
references: Surgery. 1978 Jul;84(1):127-33
references: 351839
references: J Cell Sci. 2005 Aug 15;118(Pt 16):3569-72
references: 16105880
references: Exp Mol Pathol. 2011 Aug;91(1):471-7
references: 21586283
references: Inflamm Allergy Drug Targets. 2009 Jun;8(2):110-23
references: 19530993
references: Nature. 2002 Jul 4;418(6893):41-9
references: 12077603
references: Bone Marrow Transplant. 2007 May;39(10):637-45
references: 17369865
references: Am J Respir Cell Mol Biol. 2004 Mar;30(3):396-402
references: 12959945
references: Cell Transplant. 2009;18(4):433-41
references: 19622230
references: PLoS One. 2011 Jan 28;6(1):e16509
references: 21305051
references: Ann Biomed Eng. 1998 Mar-Apr;26(2):181-9
references: 9525759
references: J Mater Sci Mater Med. 1998 Apr;9(4):197-202
references: 15348892
references: Gene. 2013 Dec 10;532(1):1-12
references: 23246696
references: Respir Res. 2006 Apr 27;7:68
references: 16643666
references: BMC Genomics. 2012 Apr 26;13:154
references: 22537220
references: FASEB J. 2003 Oct;17(13):1800-11
references: 14519659
references: Am J Physiol. 1989 Aug;257(2 Pt 1):E261-8
references: 2548393
references: DNA Cell Biol. 2012 Aug;31(8):1403-11
references: 22553926
references: Gastroenterology. 2009 Mar;136(3):978-89
references: 19135996
references: Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):716-23
references: 20110569
references: J Biol Chem. 2010 Jul 2;285(27):20492-8
references: 20435894
references: J Immunol. 2007 Aug 1;179(3):1855-63
references: 17641052
references: Science. 1999 Apr 2;284(5411):143-7
references: 10102814
references: Respir Res. 2010 Oct 28;11:148
references: 21029443
references: Annu Rev Physiol. 2006;68:563-83
references: 16460284
references: Exp Cell Res. 2013 Aug 1;319(13):2081-2090
references: 23693020
references: Int Immunopharmacol. 2011 Aug;11(8):1038-44
references: 21382533
references: J Cell Sci. 2011 Jun 1;124(Pt 11):1775-83
references: 21576351
references: Cell Transplant. 2009;18(9):1013-28
references: 19523328
references: EMBO Mol Med. 2009 Aug;1(5):288-95
references: 19890474
references: Int Immunopharmacol. 2005 Mar;5(3):495-502
references: 15683846
references: Stem Cells. 2008 Apr;26(4):1047-55
references: 18192235
references: Am J Physiol Lung Cell Mol Physiol. 2003 Aug;285(2):L464-75
references: 12716652
references: Transl Res. 2011 Apr;157(4):180-90
references: 21420028
references: Am J Physiol Lung Cell Mol Physiol. 2011 Oct;301(4):L536-46
references: 21724858
references: Biomaterials. 2013 Jan;34(4):1311-26
references: 23137393
references: J Biol Chem. 2011 Apr 1;286(13):11604-15
references: 21282106
references: FASEB J. 2006 Mar;20(3):455-65
references: 16507763
references: J Gene Med. 2008 Jun;10(6):668-78
references: 18361478
references: Mol Biol Evol. 2009 Jun;26(6):1195-8
references: 19299536
references: Curr Opin Allergy Clin Immunol. 2012 Feb;12(1):49-52
references: 22157155
references: J Allergy Clin Immunol. 2000 Oct;106(4):615-24
references: 11031329
references: Am J Physiol Gastrointest Liver Physiol. 2010 Nov;299(5):G1187-97
references: 20829523
references: PLoS One. 2010 Apr 26;5(4):e10088
references: 20436665
references: Zhonghua Jie He He Hu Xi Za Zhi. 2006 Oct;29(10):688-93
references: 17129497
references: Hum Gene Ther. 2010 Jun;21(6):713-27
references: 20102275
references: Ups J Med Sci. 1992;97(2):127-39
references: 1471312
references: Am J Physiol Lung Cell Mol Physiol. 2010 Dec;299(6):L760-70
references: 20817776
references: Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7113-8
references: 19359473
references: Crit Care. 2011;15(5):R208
references: 21914176
references: J Cell Physiol. 2007 Jan;210(1):133-43
references: 16998809
references: Mol Ther. 2010 Jul;18(7):1365-72
references: 20389289
references: Colloids Surf B Biointerfaces. 2007 Aug 1;58(2):271-7
references: 17499488