PMID- 27780843
OWN - NLM
STAT- MEDLINE
DCOM- 20170707
LR  - 20181025
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Linking)
VI  - 131
IP  - 1
DP  - 2017 Jan 1
TI  - Binding of anti-dsDNA antibodies to proximal tubular epithelial cells contributes 
      to renal tubulointerstitial inflammation.
PG  - 49-67
AB  - Immune deposits are often observed along the tubular basement membrane in 
      patients with lupus nephritis, but the role of anti-dsDNA antibody (Ab) 
      deposition on tubulointerstitial inflammation remains to be investigated. We 
      examined the effect of human polyclonal anti-dsDNA Abs on inflammatory processes 
      in cultured proximal renal tubular epithelial cells (PTEC, HK-2 cells) and their 
      association with serum levels of interleukin (IL)-6, IL-8 and monocyte 
      chemoattractant protein-1 (MCP-1) in patients. Binding of anti-dsDNA Abs to HK-2 
      cells was investigated by cellular ELISA, flow cytometry and 
      immunohistochemistry. IL-6, IL-8 and MCP-1 secretion, mitogen-activated protein 
      kinase (MAPK) activation and the effect of mycophenolic acid (MPA) were 
      investigated by ELISAs and Western blot analysis. NZBWF1/J mice with active 
      nephritis were randomized to receive either mycophenolate mofetil (MMF) 
      (100 mg/kg per day) or vehicle for up to 12 weeks to study renal histopathology 
      focusing on tubulointerstitial changes. Our results demonstrated that anti-dsDNA 
      Abs bound to HK-2 cell surface and induced IL-6, IL-8 and MCP-1 secretion through 
      distinct MAPK pathways. MPA inhibited anti-dsDNA Ab binding to HK-2 cells and 
      suppressed apical and basolateral IL-6 and IL-8, but not MCP-1, secretion. 
      Anti-dsDNA Ab level correlated with serum and tubulointerstitial expression of 
      IL-6, IL-8 and MCP-1. MMF treatment in NZBWF1/J mice reduced anti-dsDNA Ab 
      production and MAPK activation in the renal tubulointerstitium, together with 
      decreased IL-6 and MCP-1 expression. Our data demonstrate that anti-dsDNA Abs 
      contribute to inflammatory processes in the tubulointerstitium in lupus nephritis 
      through their binding to proximal renal tubular epithelial cells and induction of 
      pro-inflammatory mediators, and MPA ameliorates anti-dsDNA Ab induced IL-6 and 
      IL-8 secretion in these cells.
CI  - (c) 2016 The Author(s). published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Yung, Susan
AU  - Yung S
AD  - Department of Medicine, The University of Hong Kong, Hong Kong dtmchan@hku.hk 
      ssyyung@hku.hk.
FAU - Ng, Claudia Y C
AU  - Ng CY
AD  - Department of Medicine, The University of Hong Kong, Hong Kong.
FAU - Au, Kin Yi
AU  - Au KY
AD  - Department of Medicine, The University of Hong Kong, Hong Kong.
FAU - Cheung, Kwok Fan
AU  - Cheung KF
AD  - Department of Medicine, The University of Hong Kong, Hong Kong.
FAU - Zhang, Qing
AU  - Zhang Q
AD  - Department of Medicine, The University of Hong Kong, Hong Kong.
FAU - Zhang, Chenzhu
AU  - Zhang C
AD  - Department of Medicine, The University of Hong Kong, Hong Kong.
FAU - Yap, Desmond Y H
AU  - Yap DY
AD  - Department of Medicine, The University of Hong Kong, Hong Kong.
FAU - Chau, Mel K M
AU  - Chau MK
AD  - Department of Medicine, The University of Hong Kong, Hong Kong.
FAU - Chan, Tak Mao
AU  - Chan TM
AD  - Department of Medicine, The University of Hong Kong, Hong Kong dtmchan@hku.hk 
      ssyyung@hku.hk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161025
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (Autoantibodies)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Autoantibodies/*immunology
MH  - DNA/*immunology
MH  - Epithelial Cells/*immunology
MH  - Female
MH  - Humans
MH  - Interleukin-6/immunology
MH  - Interleukin-8/immunology
MH  - Kidney Tubules, Proximal/*immunology
MH  - Lupus Nephritis/*immunology
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Mitogen-Activated Protein Kinases/immunology
OTO - NOTNLM
OT  - anti-dsDNA antibodies
OT  - cytokines
OT  - lupus nephritis
OT  - mitogen-activated protein kinase (MAPK)
OT  - mycophenolic acid
OT  - proximal renal tubular epithelial cells
EDAT- 2016/11/01 06:00
MHDA- 2017/07/08 06:00
CRDT- 2016/11/01 06:00
PHST- 2016/06/04 00:00 [received]
PHST- 2016/09/30 00:00 [revised]
PHST- 2016/10/25 00:00 [accepted]
PHST- 2016/11/01 06:00 [pubmed]
PHST- 2017/07/08 06:00 [medline]
PHST- 2016/11/01 06:00 [entrez]
AID - CS20160421 [pii]
AID - 10.1042/CS20160421 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2017 Jan 1;131(1):49-67. doi: 10.1042/CS20160421. Epub 2016 Oct 
      25.