A Novel Immunomodulatory Protein from Poria cocos Induces Toll-like Receptor 4-Dependent Activation within Mouse Peritoneal Macrophages

2009 ◽  
Vol 57 (14) ◽  
pp. 6129-6139 ◽  
Author(s):  
Hui-Hsin Chang ◽  
Chen-Hao Yeh ◽  
Fuu Sheu
Keyword(s):  
Peritoneal Macrophages ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Poria Cocos ◽  
Immunomodulatory Protein ◽  
Mouse Peritoneal Macrophages

scholarly journals Bacteroides fragilis-Derived Lipopolysaccharide Produces Cell Activation and Lethal Toxicity via Toll-Like Receptor 4

2005 ◽  
Vol 73 (9) ◽  
pp. 5620-5627 ◽  
Author(s):  
Giuseppe Mancuso ◽  
Angelina Midiri ◽  
Carmelo Biondo ◽  
Concetta Beninati ◽  
Maria Gambuzza ◽  
...  
Keyword(s):  
Cell Activation ◽  
Cytokine Production ◽  
Biological Activities ◽  
Endotoxic Shock ◽  
Intestinal Flora ◽  
Bacteroides Fragilis ◽  
Peritoneal Macrophages ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
In Cells

ABSTRACT Bacteroides fragilis, which is part of the normal intestinal flora, is a frequent cause of serious disease, especially in diabetic and surgical patients. In these conditions, B. fragilis lipopolysaccharide (LPS) is likely to play a major pathophysiologic role. B. fragilis LPS is structurally different from classical enterobacterial LPS, whose biological activities are mediated by Toll-like receptor 4 (TLR4) activation. The ability of B. fragilis LPS to activate TLR4 and TLR2 was investigated here, since evidence on this issue is scarce and controversial. Each of four different protein-free B. fragilis LPS preparations could induce interleukin-8 responses in cells cotransfected with TLR4/CD14/MD2 but not TLR4/CD14 alone. Two of the preparations also induced cytokine production in cells cotransfected with TLR2/CD14 or in peritoneal macrophages from TLR4 mutant C3H/HeJ mice. Both of these activities, however, were lost after repurification with a modified phenol reextraction procedure. Importantly, all preparations could induce endotoxic shock in TLR2-deficient mice, but not in TLR4 mutant C3H/HeJ mice. Consistent with these findings, anti-TLR4 and anti-CD14, but not anti-TLR2, antibodies could inhibit B. fragilis LPS-induced cytokine production in human monocytes. Collectively, these results indicate that B. fragilis LPS signals via a TLR4/CD14/MD2-dependent pathway, and it is unable to activate TLR2. Moreover, our data document the occurrence of TLR2-activating contaminants even in highly purified B. fragilis LPS preparations. This may explain earlier contradictory findings on the ability of B. fragilis LPS to activate cells in the absence of functional TLR4. These data may be useful to devise strategies to prevent the pathophysiologic changes observed during B. fragilis sepsis and to better understand structure-activity relationships of LPS.

scholarly journals Induction of TNF-α and MnSOD by endotoxin: role of membrane CD14 and Toll-like receptor-4

2001 ◽  
Vol 280 (6) ◽  
pp. C1422-C1430 ◽  
Author(s):  
Min-Fu Tsan ◽  
Robert N. Clark ◽  
Sanna M. Goyert ◽  
Julie E. White
Keyword(s):  
Manganese Superoxide Dismutase ◽  
Nuclear Factor Κb ◽  
Peritoneal Macrophages ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Potent Inducer ◽  
Tnf Α ◽  
Tlr4 Gene

Endotoxin (LPS) is a potent inducer of tumor necrosis factor-α (TNF-α) and manganese superoxide dismutase (MnSOD). Recent evidence suggests that LPS induction of TNF-α and MnSOD mRNAs is mediated through distinct intracellular signal transduction pathways. Membrane CD14 (mCD14) and Toll-like receptor-4 (TLR4) mediate LPS induction of TNF-α in macrophages. In the current study, we evaluated the role of mCD14 and TLR4 in LPS induction of MnSOD using peritoneal macrophages from CD14 knockout (CD14-KO) mice and mice with the Tlr4 gene point mutation (C3H/HeJ) or deletion (C57BL/10ScCr). We studied mCD14-dependent (1 and 10 ng/ml) and mCD14-independent (1,000 ng/ml) concentrations of LPS. Compared with control (BALB/c) macrophages, LPS at 1 and 10 ng/ml failed to induce TNF-α or MnSOD mRNA in CD14-KO macrophages. However, LPS at 1,000 ng/ml induced TNF-α and MnSOD mRNAs equally in macrophages from CD14-KO and control mice. LPS (1, 10, or 1,000 ng/ml) failed to induce TNF-α or MnSOD mRNA and failed to activate nuclear factor-κB in C3H/HeJ or C57BL/10ScCr macrophages. Measurements of TNF-α and MnSOD enzyme activity paralleled TNF-α and MnSOD mRNA levels. These data demonstrate that, like TNF-α, induction of MnSOD by LPS is mediated by mCD14 and TLR4 in murine macrophages.

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