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Interleukin 6 derived from macrophages enhances angiotensinogen expression in renal proximal tubular cells (1173.3)
Author(s) -
Satou Ryousuke,
Miyata Kayoko,
Navar L. Gabriel
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1173.3
Subject(s) - olmesartan , angiotensin ii , endocrinology , medicine , angiotensin ii receptor type 1 , renin–angiotensin system , chemistry , stimulation , kidney , incubation , receptor , blood pressure , biochemistry
Chronic angiotensin II (Ang II) infusion leads to hypertension, intrarenal renin‐angiotensin system activation, stimulation of proximal tubular AGT and renal MΦ infiltration. Treatment with immunosuppressive drugs reduces MΦs infiltration, intrarenal Ang II levels and blood pressure, suggesting that MΦ contribute to intrarenal RAS activation and hypertension. However, the contribution of MΦ to AGT augmentation has not been delineated. To elucidate the role of MΦ in AGT augmentation, cultured rat MΦ were treated with 0.05‐5 μM Ang II up to 48 h. After removal of MΦ, the culture medium was incubated with rat PTC for 24 h. mRNA levels of interleukin 6 (IL‐6) in MΦ and AGT in PTC were evaluated by real‐time RT‐PCR. Treatment with 5 μM Ang II activated p38 MAP kinase and increased IL‐6 expression (2.65 ± 0.11, ratio to control) at 48 h; this response was attenuated by AT1 receptor blockade with olmesartan. Incubation of PTC with the culture medium of Ang II‐stimulated MΦ increased AGT expression in PTC (1.71 ± 0.49 by 5 μM Ang II). A neutralizing IL‐6 antibody added to culture medium attenuated the AGT augmentation in PTC (1.17 ± 0.27). These results demonstrate that Ang II mediated increases in IL‐6 production by MΦ increase AGT expression in PTC, suggesting that the Ang II mediated accumulation of MΦ in the kidney stimulates IL‐6 production in the MΦ, which augments intrarenal AGT expression contributing to hypertension.