PMID- 30536556
OWN - NLM
STAT- MEDLINE
DCOM- 20200511
LR  - 20200511
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 234
IP  - 7
DP  - 2019 Jul
TI  - Uric acid and angiotensin II additively promote inflammation and oxidative stress 
      in human proximal tubule cells by activation of toll-like receptor 4.
PG  - 10868-10876
LID - 10.1002/jcp.27929 [doi]
AB  - Renal proximal tubular cells (PTECs) participate in several mechanisms of innate 
      immunity, express toll-like receptors (TLRs), and proinflammatory cytokines. 
      Hyperuricemia may be a promoter of inflammation and renal damage. Angiotensin II 
      (Ang II) modulate immune and inflammatory responses in renal tubular cells. With 
      the aim to evaluate the effect of uric acid (UA) and Ang II on oxidative stress 
      and inflammation mediated by toll-like receptor 4 (TLR4) activation in human 
      PTECs, human kidney 2 (HK2) were incubated for 24 hr with UA (12 mg/dl) and Ang 
      II (10 (-7)  M). HK2 were pretreated with an antagonist of TLR4 (TAK 242), 
      valsartan or losartan. The genic expression of TLR4, monocyte chemoattractant 
      protein-1 (MCP1), and Nox4 was quantified with reverse transcription polymerase 
      chain reaction, proteins were evaluated with Western blot. The incubation of HK2 
      either with UA or with Ang II determines an increased expression of TLR4, 
      production of proinflammatory cytokines as MCP1 and pro-oxidants as Nox4 ( 
      p < 0.05). TAK 242 attenuates the expression of MCP1 induced both by UA and Ang 
      II. Valsartan attenuated all the effects we described after exposure to Ang II 
      but not those observed after UA exposure. At variance, pretreatment with 
      losartan, which inhibits UA internalization, attenuates the expression of TLR4, 
      MCP1, and Nox4 in cells previously treated with UA, Ang II, and UA plus Ang II. 
      Proinflammatory pathways are induced in an additive manner by UA and Ang II ( 
      p < 0.05) and might be mediated by TLR4 in PTECs. Renin-angiotensin-aldosterone 
      system (RAAS) activation, hyperuricemia, and innate immunity interplay in the 
      development of chronic tubular damage and the interaction of several nephrotoxic 
      mechanisms blunt the protective effect of RAAS inhibition.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Milanesi, Samantha
AU  - Milanesi S
AD  - Department of Internal Medicine, University of Genoa and Ospedale Policlinico San 
      Martino-IST, Genova, Italy.
FAU - Verzola, Daniela
AU  - Verzola D
AD  - Department of Internal Medicine, University of Genoa and Ospedale Policlinico San 
      Martino-IST, Genova, Italy.
FAU - Cappadona, Francesca
AU  - Cappadona F
AD  - Department of Internal Medicine, University of Genoa and Ospedale Policlinico San 
      Martino-IST, Genova, Italy.
FAU - Bonino, Barbara
AU  - Bonino B
AD  - Department of Internal Medicine, University of Genoa and Ospedale Policlinico San 
      Martino-IST, Genova, Italy.
FAU - Murugavel, Abitha
AU  - Murugavel A
AD  - Department of Internal Medicine, University of Genoa and Ospedale Policlinico San 
      Martino-IST, Genova, Italy.
FAU - Pontremoli, Roberto
AU  - Pontremoli R
AD  - Department of Internal Medicine, University of Genoa and Ospedale Policlinico San 
      Martino-IST, Genova, Italy.
FAU - Garibotto, Giacomo
AU  - Garibotto G
AD  - Department of Internal Medicine, University of Genoa and Ospedale Policlinico San 
      Martino-IST, Genova, Italy.
FAU - Viazzi, Francesca
AU  - Viazzi F
AUID- ORCID: 0000-0003-4219-7043
AD  - Department of Internal Medicine, University of Genoa and Ospedale Policlinico San 
      Martino-IST, Genova, Italy.
LA  - eng
PT  - Journal Article
DEP - 20181210
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Inflammation Mediators)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 11128-99-7 (Angiotensin II)
RN  - 268B43MJ25 (Uric Acid)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (NOX4 protein, human)
SB  - IM
MH  - Angiotensin II/*toxicity
MH  - Angiotensin II Type 1 Receptor Blockers/pharmacology
MH  - Cell Line
MH  - Chemokine CCL2/genetics/metabolism
MH  - Humans
MH  - Immunity, Innate/drug effects
MH  - Inflammation Mediators/*metabolism
MH  - Kidney Tubules, Proximal/*drug effects/immunology/metabolism/pathology
MH  - NADPH Oxidase 4/genetics/metabolism
MH  - Nephritis/*chemically induced/immunology/metabolism/pathology
MH  - Oxidative Stress/*drug effects
MH  - Renin-Angiotensin System/drug effects
MH  - Signal Transduction
MH  - Toll-Like Receptor 4/*agonists/genetics/metabolism
MH  - Uric Acid/*toxicity
OTO - NOTNLM
OT  - MCP1
OT  - Nox4
OT  - TLR4
OT  - angiotensin II
OT  - inflammation
OT  - innate immunity
OT  - oxidation
OT  - renal damage
OT  - uric acid
EDAT- 2018/12/12 06:00
MHDA- 2020/05/12 06:00
CRDT- 2018/12/12 06:00
PHST- 2018/05/12 00:00 [received]
PHST- 2018/10/23 00:00 [accepted]
PHST- 2018/12/12 06:00 [pubmed]
PHST- 2020/05/12 06:00 [medline]
PHST- 2018/12/12 06:00 [entrez]
AID - 10.1002/jcp.27929 [doi]
PST - ppublish
SO  - J Cell Physiol. 2019 Jul;234(7):10868-10876. doi: 10.1002/jcp.27929. Epub 2018 
      Dec 10.