Angiotensin II type 1 and type 2 receptors reciprocally modulate pro-inflammatory/ pro-fibrotic reactions in activated splenic lymphocytes.
Angiotensin II (Ang II) type 1 receptor (AT1R) has been confirmed to confer renoprotection in the progressive, immune-mediated nephritis in animal models as well as in humans. However, the relative contributions of direct AT1R blockade, indirect counteractivation of Ang II type 2 receptor (AT2R), or both, to renoprotection through AT1R antagonism remains to be clarified. Immunohistochemical studies in the nephritic kidney revealed that tubular epithelial cells and infiltrating immune cells were positive for AT1R and AT2R. In the present study, we investigated the action of Ang II on both receptors on immune cells. A subpopulation of lipopolysaccharide-activated splenic lymphocytes (mixed lymphocyte populations) was positive for AT1R and AT2R. Ang II alone could not induce gene expression of a pro-inflammatory chemokine JE or a pro-fibrotic cytokine transforming growth factor-beta1 in those cells. However, Ang II could significantly suppress the expression of both genes in those cells under AT1R blockade, and this action was mediated through AT2R. Conversely, the pro-inflammatory/pro-fibrotic gene expression could be enhanced by AT2R blockade, and this was mediated through AT1R. AT1R and AT2R expressed in activated immune cells can modulate pro-inflammatory and pro-fibrotic reactions reciprocally. In advanced immune-mediated nephritic kidneys, AT1R antagonism likely confers renoprotection via activation of AT2R.
Okada
Hirokazu
H
Department of Nephrology, Saitama Medical College, Saitama, Japan.
Watanabe
Yusuke
Y
Kobayashi
Tatsuya
T
Kikuta
Tomohiro
T
Kanno
Yoshihiko
Y
Suzuki
Hiromichi
H
D000818:Animals; D002478:Cells, Cultured; D005355:Fibrosis / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D013154:Spleen / Q000166:cytology* / Q000276:immunology* / Q000473:pathology
D044140:Receptor, Angiotensin, Type 1