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Prevention of Lipopolysaccharide‐Induced CD11b + Leukocytes Infiltration in the Kidney: Role of AT 2 Receptors
Author(s) -
Patel Sanket Niranjanbhai,
Dhande Isha S.,
Gray Elizabeth A.,
Ali Quaisar,
Hussain Tahir
Publication year - 2019
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.2019.33.1_supplement.566.1
Subject(s) - infiltration (hvac) , lipopolysaccharide , kidney , inflammation , monocyte , medicine , endocrinology , integrin alpha m , receptor antagonist , tumor necrosis factor alpha , receptor , chemistry , immunology , antagonist , physics , thermodynamics
Leukocyte infiltration plays a central role in mediating endotoxemic acute kidney injury (AKI). We have recently shown the anti‐inflammatory and reno‐protective role of angiotensin‐II type‐2 receptor (AT 2 R) activation under chronic low‐grade inflammatory condition using the obese Zucker rat model. The present study tests the hypothesis that prior activation of AT 2 R attenuates LPS‐mediated early infiltration of leukocytes, inflammation, and AKI. Mice were pre‐treated with AT 2 R agonist C21 (0.3 mg/kg), with and without AT 2 R antagonist PD123319 (5 mg/kg) prior to or concurrently with lipopolysaccharide (LPS, 5 mg/kg) challenge. Pre‐treatment with C21, but not concurrent treatment, significantly prevented the LPS‐induced renal infiltration of CD11b + leukocytes, increase in the levels of circulating and renal chemotactic cytokines, particularly interleukin‐6 (IL‐6) and markers of renal dysfunction (blood urea nitrogen and albuminuria), while preserving anti‐inflammatory interleukin‐10 (IL‐10) production. Moreover, C21 treatment in the absence of LPS increases renal and circulating IL‐10 levels. To investigate the role of IL‐10 in a cross talk between epithelial cells and monocytes, we performed in vitro conditioned media studies in human kidney proximal tubular epithelial (HK‐2) cells and human monocytes (THP‐1 cells). These studies revealed that the conditioned‐media derived from the C21‐treated HK‐2 cells reduced LPS‐induced THP‐1 TNF‐α production via IL‐10 originating from HK‐2 cells. Our findings suggest that activation of AT 2 R prior to LPS challenge prevents monocyte infiltration and inflammatory renal injury, possibly via an increase in renal IL‐10 production. Support or Funding Information This study was supported by NIH grants R01 DK117495 and R01 DK61578. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .