LPS-RS (LPS from R. sphaeroides) - TLR4 Antagonist

Standard and ultrapure lipopolysaccharide from R. sphaeroides

ABOUT

LPS from Rhodobacter sphaeroides

Lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides (LPS-RS) is a potent antagonist of toxic hexa-acylated LPS in human and murine cells [1]. It also prevents LPS-induced shock in mice [1]. Complete competitive inhibition of LPS activity is possible at a 100-fold excess of the antagonist. LPS-RS does not induce TLR4 signaling but is detected by the LAL standard endotoxin detection assay.

More details More details
 

Mode of action

LPS-RS is penta-acylated, and like other under-acylated LPS, appears to use at least two distinct mechanisms to block LPS-dependent activation of Toll-like receptor 4 (TLR4). The primary mechanism consists of direct competition between under-acylated LPS and hexa-acylated LPS for the same binding site on MD-2, while the secondary mechanism involves the ability of under-acylated LPS-MD-2 complexes to inhibit the TLR4 agonist activity of hexa-acylated LPS-MD-2 complexes [2-5].
 

Key features of LPS-RS Standard

  • LPS preparation extracted by a phenol-water mixture
  • Inhibits TLR4 activity
  • Activates TLR2, as it contains other bacterial components, such as lipoproteins
  • Detectable using the LAL assay
     

Key features of LPS-RS Ultrapure

  • LPS extracted by successive enzymatic hydrolysis steps (phenol-TEA-DOC extraction protocol [6])
  • Inhibits TLR4 activity
  • Does not activate TLR2, as contaminating lipoproteins have been removed
  • Detectable using the LAL assay

     

References:

1. Qureshi, N. et al., 1999. Nontoxic RsDPLA as a potent antagonist of toxic lipopolysaccharide. p. 687-98. In: Brade H., Opal S. M., Vogel S. N., and Morrison D. C., eds. Endotoxin in Health and Disease. Marcel Dekker, New York.
2. Coats SR. et al., 2005. MD-2 mediates the ability of tetra-acylated and penta-acylated lipopolysaccharides to antagonize Escherichia coli lipopolysaccharide at the TLR4 signaling complex. J Immunol. 175(7):4490-8.
3. Teghanemt A. et al., 2005. Molecular basis of reduced potency of underacylated endotoxins. J Immunol. 175(7):4669-76.
4. Visintin A. et al., 2005. Pharmacological inhibition of endotoxin responses is achieved by targeting the TLR4 coreceptor, MD-2. J Immunol. 175(10):6465-72.
5. Saitoh S. et al., 2004. Lipid A antagonist, lipid IVa, is distinct from lipid A in interaction with Toll-like receptor 4 (TLR4)-MD-2 and ligand-induced TLR4 oligomerization. Int Immunol. 16(7):961-9.
6. Hirschfeld M. et al., 2000. Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2. J Immunol. 165(2):618-22.

All InvivoGen products are for internal research use only, and not for human or veterinary use.

LPS variations and TLR4 modulation
LPS variations and TLR4 modulation

More information

Learn more about TLR4 and its co-receptors 

SPECIFICATIONS

Specifications

Source
Rhodobacter sphaeroides
Target

TLR4

Working concentration

10 ng/ml - 10 µg/ml

Solubility

5 mg/ml in water

Appearance (form)
Lyophilized
Appearance (color)
White
Reconstitution buffer
Endotoxin-free water (provided)
Tested applications

Inhibition of TLR4 cellular responses

Applications

TLR4 inhibition

Sepsis research

Quality control

Each lot is functionally tested and validated using cellular assays.

CONTENTS

Contents

  • Product: 
    LPS-RS
  • Cat code: 
    tlrl-rslps
  • Quantity: 
    5 mg
Includes:

1.5 ml endotoxin-free water

Shipping & Storage

  • Shipping method:  Room temperature

    • Storage:

    • -20 °C

    Caution:

    • Avoid repeated freeze-thaw cycles

Details

Toll-like receptor 4 (TLR4) primarily recognizes and is activated by a core component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS).  TLR4 requires interaction with a number of co-receptors including LPS-binding protein (LBP), CD14 and, myeloid differentiation protein 2 (MD-2) to bind to LPS and induce a signaling cascade. Ultimately, this leads to the activation of NF-κB and the production of pro-inflammatory cytokines.

LPS consists of a polysaccharide region that is anchored in the outer bacterial membrane by a specific carbohydrate-lipid moiety termed lipid A (also known as endotoxin). It is the lipid A region that is responsible for the immunostimulatory activity of LPS. 

Variation in lipid A, specifically the number of fatty acyl chains, among diverse bacterial species cause a vast difference in the biological activity of LPS. 

There are two major variations of lipid A:

  • Hexa-acylated (6 fatty acid chains): a highly active agonist of TLR4 and is found commonly on pathogenic bacteria such as Escherichia coli and Salmonella spp.
  • Under-acylated (4-5 fatty acid chains): induces a significantly lower host response and can be an antagonist of TLR4, by inhibiting, in a dose-dependent manner, the strong endotoxic response triggered by hexa-acylated LPS.

 

Structure of lipid A from Rhodobacter sphaeroides: 

Structure of lipid A from Rhodobacter sphaeroides

DOCUMENTS

Documents

LPS-RS

Technical Data Sheet

Safety Data Sheet

Validation Data Sheet

Certificate of analysis

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