Angiotensin-(1-7) enhances angiotensin II induced phosphorylation of ERK1/2 in mouse bone marrow-derived dendritic cells

Mol Immunol. 2009 Jan;46(3):355-61. doi: 10.1016/j.molimm.2008.10.022. Epub 2008 Nov 28.


It is well known that angiotensin-(1-7) (Ang-(1-7)) counterbalances vasoconstrictive and proliferative functions of angiotensin II (Ang II), some of those actions are via inhibition of Ang II induced activation of mitogen-activated protein kinases(MAPK). This study investigated the effects of Ang-(1-7) on Ang II-mediated cell signaling pathways in mouse bone marrow-derived dendritic cells (DC). The expression of receptor Mas and angiotensin-converting enzyme-related carboxypeptidase (ACE2) mRNA was examined by reverse transcription-polymerase chain reaction (RT-PCR); activation of MAPK was detected by immunoblotting after incubation of dendritic cells with Ang II in the presence or absence of Ang-(1-7), valsartan, PD123319, and D-Ala(7)-Ang-(1-7). Ang II rapidly (5 min, 10(-7) mol/L) stimulated phosphorylation of extracellular signal-related kinase (ERK1/2); this effect was partially inhibited by Ang II type 1 (AT1) receptor antagonist valsartan and significantly attenuated by Ang II type 2 (AT2) receptor antagonist PD123319. Ang-(1-7) alone also induced phosphorylation of ERK1/2; co-treatment of Ang-(1-7) and Ang II markedly enhanced ERK1/2 phosphorylation, the enhancement was eliminated by the Ang-(1-7) receptor antagonist D-Ala(7)-Ang-(1-7). Both Ang-(1-7) and Ang II had no effect on p38 and c-Jun N-terminal kinase (JNK) phosphorylation. In conclusion, Ang II stimulates ERK1/2 phosphorylation via AT2 receptor in mouse DC, Ang-(1-7) enhances this effect. Generation of Ang-(1-7) by DC could thereby counteract on the pro-inflammatory function of locally generated Ang II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / pharmacology*
  • Angiotensin II / pharmacology*
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / enzymology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / enzymology*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Peptide Fragments / pharmacology*
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Phosphorylation / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Peptide Fragments
  • RNA, Messenger
  • Receptors, Cell Surface
  • Angiotensin II
  • Angiotensin I
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • Peptidyl-Dipeptidase A
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)