PMID- 31072913
OWN - NLM
STAT- MEDLINE
DCOM- 20200701
LR  - 20200701
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 39
IP  - 5
DP  - 2019 May 31
TI  - Prevention of lipopolysaccharide-induced CD11b(+) immune cell infiltration in the 
      kidney: role of AT(2) receptors.
LID - BSR20190429 [pii]
LID - 10.1042/BSR20190429 [doi]
AB  - Immune cell infiltration plays a central role in mediating endotoxemic acute 
      kidney injury (AKI). Recently, we have reported the anti-inflammatory and 
      reno-protective role of angiotensin-II type-2 receptor (AT(2)R) activation under 
      chronic low-grade inflammatory condition in the obese Zucker rat model. However, 
      the role of AT(2)R activation in preventing lipopolysaccharide (LPS)-induced 
      early infiltration of immune cells, inflammation and AKI is not known. Mice were 
      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 LPS (5 mg/kg) challenge. 
      Prior-treatment with C21, but not concurrent treatment, significantly prevented 
      the LPS-induced renal infiltration of CD11b(+) immune cells, increase in the 
      levels of circulating and/or renal chemotactic cytokines, particularly 
      interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) 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 increased 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 (CM) studies in human kidney proximal 
      tubular epithelial (HK-2) cells and macrophages (differentiated 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 tumor necrosis factor-alpha (TNF-alpha) 
      production via IL-10 originating from HK-2 cells. Our findings suggest that prior 
      activation of AT(2)R is prophylactic in preventing LPS-induced renal immune cell 
      infiltration and dysfunction, possibly via IL-10 pathway.
CI  - (c) 2019 The Author(s).
FAU - Patel, Sanket
AU  - Patel S
AUID- ORCID: 0000-0003-1674-711X
AD  - Heart and Kidney Institute, Department of Pharmacological and Pharmaceutical 
      Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, U.S.A.
FAU - Dhande, Isha
AU  - Dhande I
AD  - Heart and Kidney Institute, Department of Pharmacological and Pharmaceutical 
      Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, U.S.A.
FAU - Gray, Elizabeth Alana
AU  - Gray EA
AD  - Heart and Kidney Institute, Department of Pharmacological and Pharmaceutical 
      Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, U.S.A.
FAU - Ali, Quaisar
AU  - Ali Q
AD  - Heart and Kidney Institute, Department of Pharmacological and Pharmaceutical 
      Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, U.S.A.
FAU - Hussain, Tahir
AU  - Hussain T
AUID- ORCID: 0000-0002-6353-2317
AD  - Heart and Kidney Institute, Department of Pharmacological and Pharmaceutical 
      Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, U.S.A. 
      thussain@central.uh.edu.
LA  - eng
GR  - R01 DK117495/DK/NIDDK NIH HHS/United States
GR  - R01 DK061578/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190523
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (AGTR2 protein, human)
RN  - 0 (Agtr2 protein, mouse)
RN  - 0 (CD11b Antigen)
RN  - 0 (Cytokines)
RN  - 0 (ITGAM protein, human)
RN  - 0 (Itgam protein, mouse)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptor, Angiotensin, Type 2)
SB  - IM
MH  - Acute Kidney Injury/chemically induced/*immunology/pathology
MH  - Animals
MH  - CD11b Antigen/*immunology
MH  - Cell Line
MH  - Cytokines/immunology
MH  - Humans
MH  - Kidney/*immunology/pathology
MH  - Lipopolysaccharides/*toxicity
MH  - Male
MH  - Mice
MH  - Monocytes/*immunology/pathology
MH  - Rats
MH  - Rats, Zucker
MH  - Receptor, Angiotensin, Type 2/*immunology
MH  - Signal Transduction/drug effects
MH  - THP-1 Cells
PMC - PMC6533357
OTO - NOTNLM
OT  - angiotensin-II type 2 receptor
OT  - interleukin-10
OT  - lipopolysaccharide
OT  - reno-protection
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2019/05/11 06:00
MHDA- 2020/07/02 06:00
PMCR- 2019/05/24
CRDT- 2019/05/11 06:00
PHST- 2019/01/18 00:00 [received]
PHST- 2019/04/17 00:00 [revised]
PHST- 2019/05/02 00:00 [accepted]
PHST- 2019/05/11 06:00 [pubmed]
PHST- 2020/07/02 06:00 [medline]
PHST- 2019/05/11 06:00 [entrez]
PHST- 2019/05/24 00:00 [pmc-release]
AID - BSR20190429 [pii]
AID - 10.1042/BSR20190429 [doi]
PST - epublish
SO  - Biosci Rep. 2019 May 23;39(5):BSR20190429. doi: 10.1042/BSR20190429. Print 2019 
      May 31.