Experimental abdominal aortic aneurysm formation is mediated by IL-17 and attenuated by mesenchymal stem cell treatment

Ashish K. Sharma, Guanyi Lu, Andrea Jester, William F. Johnston, Yunge Zhao, Vanessa A. Hajzus, M. Reza Saadatzadeh, Gang Su, Castigliano Bhamidipati, Gaurav S. Mehta, Irving L. Kron, Victor E. Laubach, Michael P. Murphy, Gorav Ailawadi, Gilbert R. Upchurch

Research output: Contribution to journalArticle

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Abstract

Background-Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, smooth muscle activation and matrix degradation. This study tests the hypothesis that CD4+ T-cell-produced IL-17 modulates inflammation and smooth muscle cell activation, leading to the pathogenesis of AAA and that human mesenchymal stem cell (MSC) treatment can attenuate IL-17 production and AAA formation. Methods and Results-Human aortic tissue demonstrated a significant increase in IL-17 and IL-23-/- expression in AAA patients compared with control subjects as analyzed by RT-PCR and ELISA. AAA formation was assessed in C57BL/6 (wild-type; WT), IL-23-/- or IL-17 mice using an elastase-perfusion model. Heat-inactivated elastase was used as control. On days 3, 7, and 14 after perfusion, abdominal aorta diameter was measured by video micrometry, and aortic tissue was analyzed for cytokines, cell counts, and IL-17-producing CD4+ T cells. Aortic diameter and cytokine production (MCP-1, RANTES, KC, TNF-α, MIP-1α, and IFN-γ) was significantly attenuated in elastase-perfused IL-17 and IL-23-/- mice compared with WT mice on day 14. Cellular infiltration (especially IL-17-producing CD4+ T cells) was significantly attenuated in elastase-perfused IL-17 mice compared with WT mice on day 14. Primary aortic smooth muscle cells were significantly activated by elastase or IL-17 treatment. Furthermore, MSC treatment significantly attenuated AAA formation and IL-17 production in elastase-perfused WT mice. Conclusions-These results demonstrate that CD4+ T-cell-produced IL-17 plays a critical role in promoting inflammation during AAA formation and that immunomodulation of IL-17 by MSCs can offer protection against AAA formation.

Original languageEnglish (US)
JournalCirculation
Volume126
Issue number11 SUPPL.1
DOIs
StatePublished - Sep 11 2012
Externally publishedYes

Fingerprint

Interleukin-17
Abdominal Aortic Aneurysm
Mesenchymal Stromal Cells
Pancreatic Elastase
Interleukin-23
Therapeutics
T-Lymphocytes
Inflammation
Smooth Muscle Myocytes
Perfusion
Cytokines
Chemokine CCL5
Immunomodulation
Abdominal Aorta
Smooth Muscle
Cell Count
Hot Temperature
Enzyme-Linked Immunosorbent Assay

Keywords

  • abdominal aortic aneurysm
  • inflammation
  • interleukins
  • lymphocytes
  • stem cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Sharma, A. K., Lu, G., Jester, A., Johnston, W. F., Zhao, Y., Hajzus, V. A., ... Upchurch, G. R. (2012). Experimental abdominal aortic aneurysm formation is mediated by IL-17 and attenuated by mesenchymal stem cell treatment. Circulation, 126(11 SUPPL.1). https://doi.org/10.1161/CIRCULATIONAHA.111.083451

Experimental abdominal aortic aneurysm formation is mediated by IL-17 and attenuated by mesenchymal stem cell treatment. / Sharma, Ashish K.; Lu, Guanyi; Jester, Andrea; Johnston, William F.; Zhao, Yunge; Hajzus, Vanessa A.; Reza Saadatzadeh, M.; Su, Gang; Bhamidipati, Castigliano; Mehta, Gaurav S.; Kron, Irving L.; Laubach, Victor E.; Murphy, Michael P.; Ailawadi, Gorav; Upchurch, Gilbert R.

In: Circulation, Vol. 126, No. 11 SUPPL.1, 11.09.2012.

Research output: Contribution to journalArticle

Sharma, AK, Lu, G, Jester, A, Johnston, WF, Zhao, Y, Hajzus, VA, Reza Saadatzadeh, M, Su, G, Bhamidipati, C, Mehta, GS, Kron, IL, Laubach, VE, Murphy, MP, Ailawadi, G & Upchurch, GR 2012, 'Experimental abdominal aortic aneurysm formation is mediated by IL-17 and attenuated by mesenchymal stem cell treatment', Circulation, vol. 126, no. 11 SUPPL.1. https://doi.org/10.1161/CIRCULATIONAHA.111.083451
Sharma, Ashish K. ; Lu, Guanyi ; Jester, Andrea ; Johnston, William F. ; Zhao, Yunge ; Hajzus, Vanessa A. ; Reza Saadatzadeh, M. ; Su, Gang ; Bhamidipati, Castigliano ; Mehta, Gaurav S. ; Kron, Irving L. ; Laubach, Victor E. ; Murphy, Michael P. ; Ailawadi, Gorav ; Upchurch, Gilbert R. / Experimental abdominal aortic aneurysm formation is mediated by IL-17 and attenuated by mesenchymal stem cell treatment. In: Circulation. 2012 ; Vol. 126, No. 11 SUPPL.1.
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abstract = "Background-Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, smooth muscle activation and matrix degradation. This study tests the hypothesis that CD4+ T-cell-produced IL-17 modulates inflammation and smooth muscle cell activation, leading to the pathogenesis of AAA and that human mesenchymal stem cell (MSC) treatment can attenuate IL-17 production and AAA formation. Methods and Results-Human aortic tissue demonstrated a significant increase in IL-17 and IL-23-/- expression in AAA patients compared with control subjects as analyzed by RT-PCR and ELISA. AAA formation was assessed in C57BL/6 (wild-type; WT), IL-23-/- or IL-17 mice using an elastase-perfusion model. Heat-inactivated elastase was used as control. On days 3, 7, and 14 after perfusion, abdominal aorta diameter was measured by video micrometry, and aortic tissue was analyzed for cytokines, cell counts, and IL-17-producing CD4+ T cells. Aortic diameter and cytokine production (MCP-1, RANTES, KC, TNF-α, MIP-1α, and IFN-γ) was significantly attenuated in elastase-perfused IL-17 and IL-23-/- mice compared with WT mice on day 14. Cellular infiltration (especially IL-17-producing CD4+ T cells) was significantly attenuated in elastase-perfused IL-17 mice compared with WT mice on day 14. Primary aortic smooth muscle cells were significantly activated by elastase or IL-17 treatment. Furthermore, MSC treatment significantly attenuated AAA formation and IL-17 production in elastase-perfused WT mice. Conclusions-These results demonstrate that CD4+ T-cell-produced IL-17 plays a critical role in promoting inflammation during AAA formation and that immunomodulation of IL-17 by MSCs can offer protection against AAA formation.",
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AU - Sharma, Ashish K.

AU - Lu, Guanyi

AU - Jester, Andrea

AU - Johnston, William F.

AU - Zhao, Yunge

AU - Hajzus, Vanessa A.

AU - Reza Saadatzadeh, M.

AU - Su, Gang

AU - Bhamidipati, Castigliano

AU - Mehta, Gaurav S.

AU - Kron, Irving L.

AU - Laubach, Victor E.

AU - Murphy, Michael P.

AU - Ailawadi, Gorav

AU - Upchurch, Gilbert R.

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