Mechanisms of the antitumoral effect of lipid A

Reisser, D; Pance, Alena; Jeannin, Jean–François

doi:10.1002/bies.10053

Cited by 58 publications

(47 citation statements)

References 63 publications

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“…Furthermore, the biological activities of lipid A are not limited to endotoxin signaling pathways. It can also interfere with other intracellular signaling mechanisms, 28 and intervene with and inhibit the glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) signaling pathway. 29 This inhibition is a specific process that is probably due to binding of the lipid A structure at the substrate-binding site of the enzyme.…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein-bound endotoxin exerts an immunomodulatory effect on hepatocytes through the lipid A domain of LPS

Kasravi¹,

Lee²,

Weisgraber³

et al. 2005

J. Endotoxin Res.

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Section: Discussionmentioning

confidence: 99%

Lipoprotein-bound endotoxin exerts an immunomodulatory effect on hepatocytes through the lipid A domain of LPS

Kasravi¹,

Lee²,

Weisgraber³

et al. 2005

J. Endotoxin Res.

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“…Taken together, the induction of tolerance by using MAbs against TLR4 could be a novel potentially therapeutic strategy for endotoxin shock. Moreover, UT12 might be used as an immune activator, because TLR4 agonists are used for such purposes as adjuvants of vaccination (17) and antitumor reagents (21). Accordingly, UT12 provides the prospect for the use of agonistic anti-TLR4 MAbs for clinical applications.…”

Section: Ut12 Induces Long-term Lps Tolerance In Vivomentioning

confidence: 99%

Induction of Long-Term Lipopolysaccharide Tolerance by an Agonistic Monoclonal Antibody to the Toll-Like Receptor 4/MD-2 Complex

Bahrun¹,

Shimazu²,

Matsushita³

et al. 2006

Clin Vaccine Immunol

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We have established an agonistic monoclonal antibody, UT12, that induces stimulatory signals comparable to those induced by lipopolysaccharide (LPS) through Toll-like receptor 4 and MD-2. UT12 activated nuclear factor B and induced the production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-␣) and interleukin-6 (IL-6) in peritoneal exudative cells. In addition, mice injected with UT12 rapidly fell into endotoxin shock concomitant with the augmentation of serum TNF-␣ and IL-6 levels, followed by death within 12 h. On the other hand, when the mice were pretreated with a sublethal dose of UT12, the mice survived the subsequent lethal LPS challenges, with significant suppression of serum TNF-␣ and IL-6, indicating that UT12 induced tolerance against LPS. This effect of UT12 was maintained for at least 9 days. In contrast, the tolerance induced by LPS continued for less than 3 days. These results illuminate a novel potential therapeutic strategy for endotoxin shock by the use of monoclonal antibodies against the Toll-like receptor 4/MD-2 complex.Lipopolysaccharide (LPS) is a glycolipid component of the gram-negative bacterial cell wall and induces various host responses, including the production of proinflammatory cytokines. When they are appropriately produced, these cytokines, such as tumor necrosis factor alpha (TNF-␣) and interleukin-6 (IL-6), activate host immunity to fight off bacteria. The excessive proinflammatory cytokines produced in response to large amounts of LPS, however, can provoke extreme systemic inflammation and often cause lethal endotoxin shock.Animals pretreated with a sublethal dose of LPS become tolerant to subsequent challenges with a lethal dose of LPS and display reduced mortality. This phenomenon is called LPS tolerance and is defined as the reduced capacity of the host or cultured macrophage/monocyte to respond to LPS following initial stimulation (6,26). It has also been reported that bacterial or fungal removal is improved during the tolerant state, despite attenuated cytokine production (14,20). Therefore, LPS tolerance is regarded as a reasonable response that simultaneously manages both the clearance of pathogens and host protection from excess inflammation.Here we report on the induction of long-term LPS tolerance realized by an agonistic monoclonal antibody (MAb) against the Toll-like receptor 4 (TLR4)/MD-2 complex. Mice pretreated with this MAb showed significant survival advantages compared with the survival of LPS-pretreated mice. MATERIALS AND METHODSMice. C3H/HeN, C3H/HeJ, ddY, and SCID mice were from Japan SLC (Hamamatsu, Shizuoka, Japan). C57BL/6 mice were from Charles River Japan (Yokohama, Kanagawa, Japan). A TLR4-knockout mouse strain with the C57BL/6 background (12) was a kind gift from S. Akira (Osaka University, Osaka, Japan). All animals were maintained in the Center for Laboratory Animals at Saga Medical School and were treated in accordance with the regulations of the Scientists Center for Animal Welfare.Cell culture. All the cells were cult...

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“…Its anti-tumor effect has been demonstrated in animals as well as in clinical trials. 34 Lipotechoic acid (LTA) from Streptococcus pyogenes and Entercoccous faecalis has had a tumor protective effect both, alone and in combination with peptidoglycan of Moraxella catarrhalis and LPS from E. coli. This ability of LTA to enhance and/or amplify the anti-tumor mechanisms induced by primary stimuli may be related to its capability to trigger in vitro long-lasting anti-tumor activity in bone marrow macrophages.…”

Section: Bacteria-derived Anti-cancer Agentsmentioning

confidence: 99%

Microbial based therapy of cancer: A new twist to an age old practice

Punj

Saint‐Dic²,

Daghfal³

et al. 2004

Cancer Biology & Therapy

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The use of bacteria in the regression of tumors has long been known. Various approaches for using bacteria in cancer therapy include the use of bacteria as sensitizing agents for chemotherapy, as delivery agents for cancer drugs and as agents for gene therapy. The tumor regression stimulated by infecting microorganisms has been attributed to activation of the immune system of the host. However, recent studies indicate that when tumorharboring mice with defective immune systems are infected with certain microorganisms, the regression of the tumor is still observed, suggesting that there are other host factors contributing to the microbial associated regression of tumors. Since the use of live or attenuated bacteria for tumor regression has associated toxic effects, studies are in progress to identify a pure microbial metabolite or any component of the microbial cell that might have anti-cancer activity. It has now been demonstrated that a redox protein from Pseudomonas aeruginosa, a cupredoxin, can enter into human cancer cells and trigger the apoptotic cell death. In vivo, this cupredoxin can lead to the regression of tumor growth in immunodeficient mice harboring xenografted melanomas and breast cancer tumors without inducing significant toxic effects, suggesting that it has potential anti-cancer activity. This bacterial protein interacts with p53 and modulates mammalian cellular activity. Hence, it could potentially be used as an anti-cancer agent for solid tumors and has translational value in tumor-targeted or in combinational-biochemotherapy strategies for cancer treatments. Here, we focus on diverse approaches to cancer biotherapy, including bacteriolytic and bacterially-derived anti-cancer agents with an emphasis on their mechanism of action and therapeutic potential.

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Mechanisms of the antitumoral effect of lipid A

Cited by 58 publications

References 63 publications

Lipoprotein-bound endotoxin exerts an immunomodulatory effect on hepatocytes through the lipid A domain of LPS

Lipoprotein-bound endotoxin exerts an immunomodulatory effect on hepatocytes through the lipid A domain of LPS

Induction of Long-Term Lipopolysaccharide Tolerance by an Agonistic Monoclonal Antibody to the Toll-Like Receptor 4/MD-2 Complex

Microbial based therapy of cancer: A new twist to an age old practice

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