Inhibition of Lipid A Stimulated Activation of Human Dendritic Cells and Macrophages by Amino and Hydroxylamino Monosaccharides

Peri, Francesco; Granucci, Francesca; Costa, Barbara; Zanoni, Ivan; Marinzi, Chiara; Nicotra, Francesco

doi:10.1002/ange.200604932

Cited by 7 publications

(5 citation statements)

References 25 publications

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“…Notably, (+)-naloxone has also been shown to prevent the development of opioid-induced mechanical hyperalgesia caused by intrathecal injection of M3G (Lewis et al, 2010). FP-1, a synthesized TLR4 antagonist with a monosaccharide structure (Peri et al, 2007), is another successful example with which repeated intraperitoneal injection significantly attenuated both mechanical and thermal hypersensitivity in the mouse CCI model (Bettoni et al, 2008).…”

Section: Preclinical Evidence Showing the Therapeutic Potential Of Tamentioning

confidence: 98%

Pattern recognition receptors in chronic pain: Mechanisms and therapeutic implications

Kato

Agalave

Svensson

2016

European Journal of Pharmacology

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Section: Preclinical Evidence Showing the Therapeutic Potential Of Tamentioning

confidence: 98%

Pattern recognition receptors in chronic pain: Mechanisms and therapeutic implications

Kato

Agalave

Svensson

2016

European Journal of Pharmacology

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“…Also, IgG-mediated reaction, which was associated with anaphylaxis (41), is one of major problems for its clinical use. Alternatively, small molecules targeting CD14, such as IAXO-101 and VB-201, might be other possible alternatives, but their actions are restricted to TLR2 and TLR4 (27,28). From these viewpoints, the inhibitory effects on multiple TLRs of MHP1-AcN are unique and might be more suitable for the treatment of ALI than the currently used agents.…”

Section: Discussionmentioning

confidence: 99%

“…For example, CD14 directly binds to LPS and controls the trafficking and signaling functions of TLR4 (23,24). However, anti-CD14 Abs failed to decrease the inflammatory response consistently in patients experiencing severe sepsis (25,26), and small molecules targeting CD14 are restricted to TLR4 (27) or TLR2/ 4 signaling (28).…”

Section: Introductionmentioning

confidence: 99%

Prevention of Acute Lung Injury by a Novel CD14-Inhibitory Receptor Activator of the NF-κB Ligand Peptide in Mice

Hayashi

Shimamura

et al. 2021

ImmunoHorizons

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Although CD14 has been implicated in the initiation of multiple TLR-mediated inflammatory responses to sepsis and sepsis-related acute lung injury (ALI), an inhibitor of CD14, except for neutralizing Abs, has not been developed. A partial peptide, microglial healing peptide 1 with N-terminal acetylation and C-terminal amidation (MHP1-AcN), derived from the receptor activator of the NF-rB ligand, was recently found to inhibit multiple TLR signaling in the macrophages. Therefore, we hypothesized that the inhibitory effect of MHP1-AcN might be through the inhibition of CD14, a common coreceptor for multiple TLRs. In cultured mouse macrophages, MHP1-AcN was shown to bind to CD14 and compete with LPS for competitive inhibition of CD14, resulting in inhibition of TLR4 signaling, including NF-rB and IFN regulatory factor 3 activation and nuclear translocation. In addition to TLR2, TLR4, and TLR7, MHP1-AcN also inhibited TLR3 signaling and Escherichia coli DNA-induced, CD14-dependent TLR9 signals; however, CpG oligodeoxynucleotide-induced, CD14-independent TLR9 signals were not inhibited in the mouse macrophages. In sepsis-induced ALI mouse model, MHP1-AcN treatment showed the reduction in the expression of IL-6 and CCL2 in both the serum and lung tissues. IL-6 levels in the bronchoalveolar lavage fluid and pathological score were also decreased by MHP1-AcN. Thus, MHP1-AcN, a novel CD14 inhibitor, could be a promising agent for treating sepsis-induced ALI. ImmunoHorizons, 2021, 5: 438-447.

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“…TLR4-A1 (CAS RN: 1202208-36-3) is a synthetic benzylammonium ether lipid designed like a non-hydrolysable structural analogue of LipoPolySaccharide (LPS), the naturally occurring ligand of TLR4 ( Figure 1 ). Based on recent studies (both in vitro 32 , 33 and in vivo 28 ), this compound proved to be an effective inhibitor of the TLR4 activation pathway. The authors reported that TLR4-A1 inhibited LPS-induced TLR4 activation in HEK293 stably transfected with TLR4, MD-2 and CD14 gene.…”

Section: Methodsmentioning

confidence: 99%

TLR4 Antagonism Reduces Movement-Induced Nociception and ATF-3 Expression in Experimental Osteoarthritis

Ferreira‐Gomes

García

Nascimento

et al. 2021

JPR

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Introduction Toll-like receptor 4 (TLR4) is a pattern recognition receptor involved in the detection of pathogen-associated molecular patterns (PAMPs), but also a “danger-sensing” receptor that recognizes host-derived endogenous molecules called damage-associated molecular patterns (DAMPs). The involvement of TLR4 in rheumatic diseases is becoming evident, as well as its potential role as a target for therapeutic intervention. Moreover, increasing evidence also suggests that TLR4 is implicated in chronic pain states. Thus, in this study, we evaluated whether a systemic administration of a synthetic antagonist of TLR4 (TLR4-A1) could decrease nociception and cartilage degradation in experimental osteoarthritis (OA). Furthermore, as the activation transcription factor (ATF)-3 serves as a negative regulator for TLR4-stimulated inflammatory response, we also evaluated the effect of TLR4 inhibition on ATF-3 expression in primary afferent neurons at the dorsal root ganglia (DRG). Methods OA was induced in adult male Wistar rats through an intra-articular injection of 2 mg of sodium mono-iodoacetate (MIA) into the left knee. From days 14 to 28 after OA induction, animals received an intraperitoneal injection of either TLR4-A1 (10 mg/kg) or vehicle. Movement- and loading-induced nociception was evaluated in all animals, by the Knee-Bend and CatWalk tests, before and at several time-points after TLR4-A1/vehicle administration. Immunofluorescence for TLR4 and ATF-3 was performed in L3-L5 DRG. Knee joints were processed for histopathological evaluation. Results Administration of TLR4-A1 markedly reduced movement-induced nociception in OA animals, particularly in the Knee-Bend test. Moreover, the increase of ATF-3 expression observed in DRG of OA animals was significantly reduced by TLR4-A1. However, no effect was observed in cartilage loss nor in the neuronal cytoplasmic expression of TLR4 upon antagonist administration. Conclusion The TLR4 antagonist administration possibly interrupts the TLR4 signalling cascade, thus decreasing the neurotoxic environment at the joint, which leads to a reduction in ATF-3 expression and in nociception associated with experimental OA.

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Inhibition of Lipid A Stimulated Activation of Human Dendritic Cells and Macrophages by Amino and Hydroxylamino Monosaccharides

Cited by 7 publications

References 25 publications

Pattern recognition receptors in chronic pain: Mechanisms and therapeutic implications

Pattern recognition receptors in chronic pain: Mechanisms and therapeutic implications

Prevention of Acute Lung Injury by a Novel CD14-Inhibitory Receptor Activator of the NF-κB Ligand Peptide in Mice

TLR4 Antagonism Reduces Movement-Induced Nociception and ATF-3 Expression in Experimental Osteoarthritis

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