PMID- 12138134
OWN - NLM
STAT- MEDLINE
DCOM- 20021227
LR  - 20190607
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 13
IP  - 8
DP  - 2002 Aug
TI  - The Leptospira outer membrane protein LipL32 induces tubulointerstitial 
      nephritis-mediated gene expression in mouse proximal tubule cells.
PG  - 2037-45
AB  - Tubulointerstitial nephritis is a main renal manifestation caused by pathogenic 
      leptospira that accumulate mostly in the proximal tubules, thereby inducing 
      tubular injury and tubulointerstitial nephritis. To elucidate the role of 
      leptospira outer membrane proteins in tubulointerstitial nephritis, outer 
      membrane proteins from pathogenic Leptospira shermani and nonpathogenic 
      Leptospira patoc extracted by Triton X-114 were administered to cultured mouse 
      proximal tubule cells. A dose-dependent increase of monocyte chemoattractant 
      protein-1 (MCP-1), RANTES, nitrite, and tumor necrosis factor-alpha (TNF-alpha) 
      in the culture supernatant was observed 48 h after incubating Leptospira shermani 
      outer membrane proteins with mouse proximal tubule cells. RT competitive-PCR 
      experiments showed that Leptospira shermani outer membrane proteins (0.2 
      microg/ml) increased the expression of MCP-1, nitric oxide synthase (iNOS), 
      RANTES, and TNF-alpha mRNA by 3.0-, 9.4-, 2.5-, and 2.5-fold, respectively, when 
      compared with untreated cells. Outer membrane proteins extract from avirulent 
      Leptospira patoc did not induce significant effects. The pathogenic outer 
      membrane proteins extract contain a major component of a 32-kD lipoprotein 
      (LipL32), which is absent in the nonpathogenic leptospira outer membrane. An 
      antibody raised against LipL32 prevented the stimulatory effect of Leptospira 
      shermani outer membrane proteins extract on MCP-1 and iNOS mRNA expression in 
      cultured proximal tubule cells, whereas recombinant LipL32 significantly 
      stimulated the expression of MCP-1 and iNOS mRNAs and augmented nuclear binding 
      of nuclear factor-kappaB (NF-kappaB) and AP-1 transcription factors in proximal 
      tubule cells. An antibody raised against LipL32 also blunted the effects induced 
      by the recombinant LipL32. This study demonstrates that LipL32 is a major 
      component of pathogenic leptospira outer membrane proteins involved in the 
      pathogenesis of tubulointerstitial nephritis.
FAU - Yang, Chih-Wei
AU  - Yang CW
AD  - Department of Nephrology, Chang Gung Memorial Hospital, Taipei, Taiwan, Republic 
      of China. cwyang@ms1.hinet.net
FAU - Wu, Mai-Szu
AU  - Wu MS
FAU - Pan, Ming-Jeng
AU  - Pan MJ
FAU - Hsieh, Wang-Ju
AU  - Hsieh WJ
FAU - Vandewalle, Alain
AU  - Vandewalle A
FAU - Huang, Chiu-Ching
AU  - Huang CC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Antibodies)
RN  - 0 (Bacterial Outer Membrane Proteins)
RN  - 0 (LipL32 protein, Leptospira)
RN  - 0 (Lipoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factor AP-1)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Bacterial Outer Membrane Proteins/analysis/immunology/*pharmacology
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Cell Survival/drug effects
MH  - DNA/metabolism
MH  - Gene Expression/*drug effects
MH  - Kidney Tubules, Proximal/drug effects/pathology/*physiopathology
MH  - Leptospira/chemistry
MH  - Lipoproteins/analysis/immunology/*pharmacology
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Nephritis, Interstitial/*genetics/pathology/physiopathology
MH  - Recombinant Proteins/immunology
MH  - Transcription Factor AP-1/metabolism
EDAT- 2002/07/26 10:00
MHDA- 2002/12/28 04:00
CRDT- 2002/07/26 10:00
PHST- 2002/07/26 10:00 [pubmed]
PHST- 2002/12/28 04:00 [medline]
PHST- 2002/07/26 10:00 [entrez]
AID - 10.1097/01.asn.0000022007.91733.62 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2002 Aug;13(8):2037-45. doi: 
      10.1097/01.asn.0000022007.91733.62.