PMID- 17617918
OWN - NLM
STAT- MEDLINE
DCOM- 20080403
LR  - 20181113
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 9
IP  - 4
DP  - 2007
TI  - Mesangial cells of lupus-prone mice are sensitive to chemokine production.
PG  - R67
AB  - Infectious antigens may be triggers for the exacerbation of systemic lupus 
      erythematosus. The underlying mechanism causing acceleration and exacerbation of 
      lupus nephritis (LN) is largely unknown. Bacterial lipopolysaccharide (LPS) is 
      capable of inducing an accelerated model of LN in NZB/W mice, featuring diffuse 
      proliferation of glomerular resident cells. We hypothesized that mesangial cells 
      (MCs) from LN subjects are more responsive to LPS than normal subjects. Cultured 
      primary NZB/W and DBA/W (nonautoimmune disease-prone strain with MHC class II 
      molecules identical to those of NZB/W) MCs were used. Monocyte chemoattractant 
      protein-1 (MCP-1) and osteopontin (OPN) expressions either in the baseline 
      (normal culture) condition or in the presence of LPS were evaluated by real-time 
      PCR, ELISA, or western blot analysis. NF-kappaB was detected by ELISA, 
      electrophoresis mobility-shift assay, and immunofluorescence. First, either in 
      the baseline condition or in the presence of LPS, NZB/W MCs produced 
      significantly higher levels of MCP-1 and OPN than the DBA/W MC controls. Second, 
      NZB/W MCs expressed significantly higher levels of Toll-like receptor 4, myeloid 
      differentiation factor 88, and NF-kappaB than the DBA/W MC controls, both 
      receiving exactly the same LPS treatment. In conclusion, NZB/W MCs are 
      significantly more sensitive than their normal control DBA/W MCs in producing 
      both MCP-1 and OPN. With LPS treatment, the significantly elevated levels of both 
      chemokines produced by NZB/W MCs are more likely due to a significantly greater 
      activation of the Toll-like receptor 4-myeloid differentiation factor 
      88-associated NF-kappaB pathway. The observed abnormal molecular events provide 
      an intrarenal pathogenic pathway involved in an accelerated type of LN, which is 
      potentially infection triggered.
FAU - Ka, Shuk-Man
AU  - Ka SM
AD  - Department of Pathology, Tri-Service General Hospital, National Defense Medical 
      Center, Cheng-Gung Road, Taipei 114, Taiwan, ROC.
FAU - Cheng, Chao-Wen
AU  - Cheng CW
FAU - Shui, Hao-Ai
AU  - Shui HA
FAU - Wu, Wen-Mein
AU  - Wu WM
FAU - Chang, Deh-Ming
AU  - Chang DM
FAU - Lin, Yu-Chu
AU  - Lin YC
FAU - Chen, Ann
AU  - Chen A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Biomarkers)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Spp1 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 106441-73-0 (Osteopontin)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression/drug effects
MH  - Lipopolysaccharides/pharmacology
MH  - Lupus Nephritis/etiology/metabolism/*pathology
MH  - Mesangial Cells/drug effects/*metabolism/pathology
MH  - Mice
MH  - Mice, Inbred DBA
MH  - Mice, Inbred NZB
MH  - Myeloid Differentiation Factor 88/genetics/metabolism
MH  - NF-kappa B/genetics/metabolism
MH  - Osteopontin/genetics/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Toll-Like Receptor 4/genetics/metabolism
MH  - Up-Regulation
PMC - PMC2206365
EDAT- 2007/07/10 09:00
MHDA- 2008/04/04 09:00
PMCR- 2007/07/07
CRDT- 2007/07/10 09:00
PHST- 2007/03/01 00:00 [received]
PHST- 2007/05/17 00:00 [revised]
PHST- 2007/07/07 00:00 [accepted]
PHST- 2007/07/10 09:00 [pubmed]
PHST- 2008/04/04 09:00 [medline]
PHST- 2007/07/10 09:00 [entrez]
PHST- 2007/07/07 00:00 [pmc-release]
AID - ar2226 [pii]
AID - 10.1186/ar2226 [doi]
PST - ppublish
SO  - Arthritis Res Ther. 2007;9(4):R67. doi: 10.1186/ar2226.