PMID- 20043049
OWN - NLM
STAT- MEDLINE
DCOM- 20100423
LR  - 20190513
IS  - 1745-7270 (Electronic)
IS  - 1672-9145 (Linking)
VI  - 42
IP  - 1
DP  - 2010 Jan
TI  - OmpA-like protein Loa22 from Leptospira interrogans serovar Lai is cytotoxic to 
      cultured rat renal cells and promotes inflammatory responses.
PG  - 70-9
AB  - Leptospirosis renal disease is one of the common clinical manifestations of 
      leptospirosis, including acute renal failure and tubulointerstitial nephritis. 
      Outer membrane protein A-like protein Loa22 is a lipoprotein from Leptospira 
      interrogans and has been suggested to be a corresponding virulence factor. 
      However, the role of Loa22 in leptospiral nephropathy is not yet understood. In 
      the present study, we constructed a vector and artificially expressed Loa22 in 
      Escherichia coli BL21(DE)pLysS cells. After extensive purification, along with a 
      GST tag protein control, Loa22 protein was used to test the cytotoxicity in 
      cultured rat proximal tubule cells (NRK52E) and examine its effects on the 
      induction of inflammatory responses. Using morphological examination, 
      2,3-bis(2-methoxy-4- nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazoium 
      hydrixide absorbance, lactate dehydrogenase assays and an analysis of apoptosis 
      via flow cytometry, it was found that Loa22 protein mediates a direct cytotoxic 
      effect on NRK52E cells in a dose-dependent manner. Using real-time PCR, western 
      blotting and immunofluorescence, it was found that Loa22 protein upregulates the 
      expression of toll-like receptor 2 (TLR2), induces nitric oxide synthase and 
      promotes the production of nitric oxide (NO) and monocyte chemoattractant 
      protein-1 (MCP-1) by NRK52E cells. Additionally, using a TLR2 blocking antibody, 
      it was found that enhanced NO and MCP-1 production by NRK52E cells after Loa22 
      stimulation requires the activation of TLR2. Collectively, our data suggested 
      that Loa22 is a critical virulence factor of L. interrogans and is involved in 
      the leptospiral nephropathy through mediating direct cytotoxicity and enhancing 
      inflammatory responses.
FAU - Zhang, Ying
AU  - Zhang Y
AD  - Infection and Immunity Lab, West China Medical Center, Sichuan University, 
      Chengdu, China. zhangying3160812@163.com
FAU - Bao, Lang
AU  - Bao L
FAU - Zhu, Hailong
AU  - Zhu H
FAU - Huang, Bi
AU  - Huang B
FAU - Zhang, Huidong
AU  - Zhang H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Acta Biochim Biophys Sin (Shanghai)
JT  - Acta biochimica et biophysica Sinica
JID - 101206716
RN  - 0 (Bacterial Outer Membrane Proteins)
RN  - 0 (Chemokine CCL2)
RN  - 149024-69-1 (OMPA outer membrane proteins)
SB  - IM
MH  - Animals
MH  - Bacterial Outer Membrane Proteins/*toxicity
MH  - Cell Culture Techniques
MH  - Cell Survival/*drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/pharmacology
MH  - Flow Cytometry
MH  - Kidney Tubules, Proximal/pathology
MH  - Leptospira interrogans/*chemistry
MH  - Leptospirosis/*pathology
MH  - Molecular Sequence Data
MH  - Rats
MH  - Transfection
EDAT- 2010/01/01 06:00
MHDA- 2010/04/24 06:00
CRDT- 2010/01/01 06:00
PHST- 2010/01/01 06:00 [entrez]
PHST- 2010/01/01 06:00 [pubmed]
PHST- 2010/04/24 06:00 [medline]
AID - 10.1093/abbs/gmp109 [doi]
PST - ppublish
SO  - Acta Biochim Biophys Sin (Shanghai). 2010 Jan;42(1):70-9. doi: 
      10.1093/abbs/gmp109.