PMID- 20846396
OWN - NLM
STAT- MEDLINE
DCOM- 20110315
LR  - 20211020
IS  - 1471-2172 (Electronic)
IS  - 1471-2172 (Linking)
VI  - 11
DP  - 2010 Sep 16
TI  - Serum lipoproteins attenuate macrophage activation and Toll-Like Receptor 
      stimulation by bacterial lipoproteins.
PG  - 46
LID - 10.1186/1471-2172-11-46 [doi]
AB  - BACKGROUND: Chlamydia trachomatis was previously shown to express a lipoprotein, 
      the macrophage infectivity potentiator (Mip), exposed at the bacterial surface, 
      and able to stimulate human primary monocytes/macrophages through Toll Like 
      Receptor (TLR)2/TLR1/TLR6, and CD14. In PMA-differentiated THP-1 cells the 
      proinflammatory activity of Mip was significantly higher in the absence than in 
      the presence of serum. The present study aims to investigate the ability of 
      different serum factors to attenuate Mip proinflammatory activity in 
      PMA-differentiated THP-1 cells and in primary human differentiated macrophages. 
      The study was also extend to another lipoprotein, the Borrelia burgdorferi outer 
      surface protein (Osp)A. The proinflammatory activity was studied through Tumor 
      Necrosis Factor alpha (TNF-alpha) and Interleukin (IL)-8 release. Finally, TLR1/2 
      human embryonic kidney-293 (HEK-293) transfected cells were used to test the 
      ability of the serum factors to inhibit Mip and OspA proinflammatory activity. 
      RESULTS: In the absence of any serum and in the presence of 10% delipidated FBS, 
      production of Mip-induced TNF-alpha and IL-8 in PMA-differentiated THP-1 cells were 
      similar whereas they were significantly decreased in the presence of 10% FBS 
      suggesting an inhibiting role of lipids present in FBS. In the presence of 10% 
      human serum, the concentrations of TNF-alpha and IL-8 were 2 to 5 times lower than in 
      the presence of 10% FBS suggesting the presence of more potent inhibitor(s) in 
      human serum than in FBS. Similar results were obtained in primary human 
      differentiated macrophages. Different lipid components of human serum were then 
      tested (total lipoproteins, HDL, LDL, VLDL, triglyceride emulsion, apolipoprotein 
      (apo)A-I, B, E2, and E3). The most efficient inhibitors were LDL, VLDL, and apoB 
      that reduced the mean concentration of TNF-alpha release in Mip-induced macrophages 
      to 24, 20, and 2%, respectively (p < 0.0001). These lipid components were also 
      able to prevent TLR1/2 induced activation by Mip, in HEK-293 transfected cells. 
      Similar results were obtained with OspA. CONCLUSIONS: These results demonstrated 
      the ability of serum lipids to attenuate proinflammatory activity of bacterial 
      lipoproteins and suggested that serum lipoproteins interact with acyl chains of 
      the lipid part of bacterial lipoproteins to render it biologically inactive.
FAU - Bas, Sylvette
AU  - Bas S
AD  - Division of Rheumatology, Department of Internal Medicine, Geneva University 
      Hospital, 1211 Geneva 14, Switzerland. Sylvette.Bas@hcuge.ch
FAU - James, Richard W
AU  - James RW
FAU - Gabay, Cem
AU  - Gabay C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100916
PL  - England
TA  - BMC Immunol
JT  - BMC immunology
JID - 100966980
RN  - 0 (Bacterial Outer Membrane Proteins)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Lipoproteins)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Bacterial Outer Membrane Proteins/immunology/isolation & purification/*metabolism
MH  - Borrelia burgdorferi/*immunology
MH  - Cell Differentiation
MH  - Cell Line, Tumor
MH  - Chlamydia trachomatis/*immunology
MH  - Humans
MH  - Immunomodulation/drug effects
MH  - Interleukin-8/biosynthesis/genetics
MH  - Lipopolysaccharide Receptors/metabolism
MH  - Lipoproteins/immunology/isolation & purification/*metabolism
MH  - Macrophage Activation/drug effects
MH  - Serum/immunology/*metabolism
MH  - Tetradecanoylphorbol Acetate/immunology/metabolism
MH  - Toll-Like Receptors/genetics/immunology/metabolism
MH  - Tumor Necrosis Factor-alpha/biosynthesis/genetics
PMC - PMC2949775
EDAT- 2010/09/18 06:00
MHDA- 2011/03/16 06:00
PMCR- 2010/09/16
CRDT- 2010/09/18 06:00
PHST- 2010/06/18 00:00 [received]
PHST- 2010/09/16 00:00 [accepted]
PHST- 2010/09/18 06:00 [entrez]
PHST- 2010/09/18 06:00 [pubmed]
PHST- 2011/03/16 06:00 [medline]
PHST- 2010/09/16 00:00 [pmc-release]
AID - 1471-2172-11-46 [pii]
AID - 10.1186/1471-2172-11-46 [doi]
PST - epublish
SO  - BMC Immunol. 2010 Sep 16;11:46. doi: 10.1186/1471-2172-11-46.