PMID- 29923769
OWN - NLM
STAT- MEDLINE
DCOM- 20190916
LR  - 20200306
IS  - 1522-1466 (Electronic)
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 315
IP  - 5
DP  - 2018 Nov 1
TI  - Intrarenal Toll-like receptor 4 and Toll-like receptor 2 expression correlates 
      with injury in antineutrophil cytoplasmic antibody-associated vasculitis.
PG  - F1283-F1294
LID - 10.1152/ajprenal.00040.2018 [doi]
AB  - In antineutrophil cytoplasmic antibody-associated vasculitis (AAV), Toll-like 
      receptors (TLRs) may be engaged by infection-associated patterns and by 
      endogenous danger signals, linking infection and innate inflammation with this 
      autoimmune disease. This study examined intrarenal TLR2, TLR4, and TLR9 
      expression and renal injury in AAV, testing the hypothesis that increased TLR 
      expression correlates with renal injury. Patients with AAV exhibited both 
      glomerular and tubulointerstitial expression of TLR2, TLR4, and TLR9, with TLR4 
      being the most prominent in both compartments. Glomerular TLR4 expression 
      correlated with glomerular segmental necrosis and cellular crescents, with TLR2 
      expression correlating with glomerular segmental necrosis. The extent and 
      intensity of glomerular and tubulointerstitial TLR4 expression and the intensity 
      of glomerular TLR2 expression inversely correlated with the presenting estimated 
      glomerular filtration rate. Although myeloid cells within the kidney expressed 
      TLR2, TLR4, and TLR9, TLR2 and TLR4 colocalized with endothelial cells and 
      podocytes, whereas TLR9 was expressed predominantly by podocytes. The functional 
      relevance of intrarenal TLR expression was further supported by the 
      colocalization of TLRs with their endogenous ligands high-mobility group box 1 
      and fibrinogen. Therefore, in AAV, the extent of intrarenal TLR4 and TLR2 
      expression and their correlation with renal injury indicates that TLR4, and to a 
      lesser degree TLR2, may be potential therapeutic targets in this disease.
FAU - O'Sullivan, Kim M
AU  - O'Sullivan KM
AUID- ORCID: 0000-0002-3098-7948
AD  - Centre for Inflammatory Diseases, Monash University Department of Medicine , 
      Clayton, Victoria , Australia.
FAU - Ford, Sharon L
AU  - Ford SL
AD  - Centre for Inflammatory Diseases, Monash University Department of Medicine , 
      Clayton, Victoria , Australia.
FAU - Longano, Anthony
AU  - Longano A
AD  - Department of Pathology, Monash Health, Clayton, Victoria , Australia.
FAU - Kitching, A Richard
AU  - Kitching AR
AD  - Centre for Inflammatory Diseases, Monash University Department of Medicine , 
      Clayton, Victoria , Australia.
AD  - Department of Nephrology, Monash Health, Clayton, Victoria , Australia.
AD  - Department of Paediatric Nephrology, Monash Health, Clayton, Victoria , 
      Australia.
FAU - Holdsworth, Stephen R
AU  - Holdsworth SR
AD  - Centre for Inflammatory Diseases, Monash University Department of Medicine , 
      Clayton, Victoria , Australia.
AD  - Department of Nephrology, Monash Health, Clayton, Victoria , Australia.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180620
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Antibodies, Antineutrophil Cytoplasmic)
RN  - 0 (HMGB1 Protein)
RN  - 0 (HMGB1 protein, human)
RN  - 0 (PAR (protease-activated receptor)-3 receptor, human)
RN  - 0 (Receptor, PAR-1)
RN  - 0 (TLR2 protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (TLR9 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptor 9)
RN  - 9001-32-5 (Fibrinogen)
RN  - EC 1.11.1.7 (MPO protein, human)
RN  - EC 1.11.1.7 (Peroxidase)
SB  - IM
MH  - Aged
MH  - Anti-Neutrophil Cytoplasmic Antibody-Associated 
      Vasculitis/*immunology/pathology/physiopathology
MH  - Antibodies, Antineutrophil Cytoplasmic/immunology
MH  - Female
MH  - Fibrinogen/analysis
MH  - Glomerular Filtration Rate
MH  - Glomerulonephritis/*immunology/pathology/physiopathology
MH  - HMGB1 Protein/analysis
MH  - Humans
MH  - Kidney Glomerulus/*immunology/pathology/physiopathology
MH  - Male
MH  - Middle Aged
MH  - Peroxidase/immunology
MH  - Receptor, PAR-1/immunology
MH  - Severity of Illness Index
MH  - Toll-Like Receptor 2/*analysis
MH  - Toll-Like Receptor 4/*analysis
MH  - Toll-Like Receptor 9/analysis
PMC - PMC6293285
OTO - NOTNLM
OT  - Toll-like receptors
OT  - antibodies
OT  - antineutrophil cytoplasmic
OT  - autoimmunity
OT  - glomerulonephritis
OT  - vasculitis
EDAT- 2018/06/21 06:00
MHDA- 2019/09/17 06:00
PMCR- 2019/11/01
CRDT- 2018/06/21 06:00
PHST- 2018/06/21 06:00 [pubmed]
PHST- 2019/09/17 06:00 [medline]
PHST- 2018/06/21 06:00 [entrez]
PHST- 2019/11/01 00:00 [pmc-release]
AID - F-00040-2018 [pii]
AID - 10.1152/ajprenal.00040.2018 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2018 Nov 1;315(5):F1283-F1294. doi: 
      10.1152/ajprenal.00040.2018. Epub 2018 Jun 20.