The contributing role of CD14 in toll-like receptor 4 dependent neuropathic pain

Cao, Ling; Tanga, Flobert; DeLeo, Joyce A.

doi:10.1016/j.neuroscience.2008.10.004

Cited by 95 publications

(89 citation statements)

References 39 publications

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“…In contrast to inflammatory pain, treatments for neuropathic pain is lacking, and therefore is a requirement to understand its molecular pathogenesis [83]. It is now thought that the basis of neuropathic pain requires immune activation in the CNS, where the production of chemokines and cytokines triggers the expression of pain mediators such as glutamate and NO [80,[84][85][86]. Critically proinflammtory cytokines such as TNF, IL-1 and IL-6 have not been associated with the generation of normal non pathological pain, yet these mediators are all associated with conditions where pain is exadurated [78].…”

Section: Of 62mentioning

confidence: 99%

“…Animal models of neuropathic pain involve the use of L5 spinal nerve ligation and monitoring behavioural sensitivity, a hallmark of neuropathic pain [86]. The use of animal models of neuropathic pain reveal activation of microglia and astrocytes in the spinal cord and the production of IL-1β and TNFα which are important in the initiation and maintenance of neuropathic pain [82].…”

Section: Of 62mentioning

confidence: 99%

“…It is now though that the release of endogenous DAMPs following nerve damage leads to the activation of astrocytes and microglia via TLRs to increase the expression of proinflammatory cytokines and chemokines which induces the production of pain mediators [86].…”

Section: Of 62mentioning

confidence: 99%

“…It was also shown that this role of CD14 was mediated by TLR4 dependent pathways. However the endogenous ligand that triggers the CD14-TLR4 signalling pathway following nerve injury was not identified, but may include one or more of HSPs, HMGB1, and β defensins [86]. The same study also showed that spinal cord microglia become reactive following nerve injury induced neuropathic pain.…”

mentioning

confidence: 99%

“…Using knockout mice it was shown that CD14 contributes to TLR4 dependent nerve injury mediated neuropathic pain but not in the nociception of physiological pain [86]. It was also shown that this role of CD14 was mediated by TLR4 dependent pathways.…”

mentioning

confidence: 99%

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Evaluating the role of Toll-like receptors in diseases of the central nervous system

Carty

Bowie

2011

Biochemical Pharmacology

134

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A key part of the innate immune system is a network of pattern recognition receptors (PRRs) and their associated intracellular signalling pathways. Toll-like receptors (TLRs) are one such group of PRRs that detect pathogen associated molecular patterns (PAMPs). Activation of the TLRs with their respective agonists results in the activation of intracellular signalling pathways leading to the expression of proinflammatory mediators and anti-microbial effector molecules. Activation of the innate immune system through TLRs also triggers the adaptive immune response, resulting in a comprehensive immune program to eradicate invading pathogens. It is now known that immune surveillance and inflammatory responses occur in the central nervous system (CNS). Furthermore it is becoming increasingly clear that TLRs have a role in such CNS responses andare also implicated in the pathogenesis of a number of conditions in the CNS, such as Alzheimer's, stroke and multiple sclerosis. This is likely due to the generation of endogenous TLR agonists in these conditions which amplifies a detrimental neurotoxic inflammatory response. However TLRs in some situations can be neuroprotective, if triggered in a favourable context. This review aims to examine the recent literature on TLRs in the CNS thus demonstrating their importance in a range of infectious and non-infectious diseases of the brain.

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Section: Of 62mentioning

confidence: 99%

Section: Of 62mentioning

confidence: 99%

Section: Of 62mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Evaluating the role of Toll-like receptors in diseases of the central nervous system

Carty

Bowie

2011

Biochemical Pharmacology

134

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Soluble Macrophage Biomarkers Indicate Inflammatory Phenotypes in Patients With Knee Osteoarthritis

Daghestani

Pieper

Kraus

2015

Arthritis & Rheumatology

205

195

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Objective To evaluate the ability of the macrophage markers CD163 and CD14 to predict different osteoarthritis (OA) phenotypes defined by severity of joint inflammation, radiographic features and progression, and joint pain. Methods We evaluated 2 different cohorts totaling 184 patients with radiographic knee OA. These included 25 patients from a cross-sectional imaging study for whom there were data on activated macrophages in the knee joint, and 159 patients (134 with 3-year longitudinal data) from the longitudinal Prediction of Osteoarthritis Progression study. Multivariable linear regression models with generalized estimating equations were used to assess the association of CD163 and CD14 in synovial fluid (SF) and blood with OA phenotypic outcomes. Models were adjusted for age, sex, and body mass index. P values less than or equal to 0.05 were considered significant. Results SF CD14, SF CD163, and serum CD163 were associated with the abundance of activated macrophages in the knee joint capsule and synovium. SF CD14 was positively associated with severity of joint space narrowing and osteophytes in both cohorts. SF and plasma CD14 were positively associated with self-reported knee pain severity in the imaging study. Both SF CD14 and SF CD163 were positively associated with osteophyte progression. Conclusion Soluble macrophage biomarkers reflected the abundance of activated macrophages and appeared to mediate structural progression (CD163 and CD14) and pain (CD14) in OA knees. These data support the central role of inflammation as a determinant of OA severity, progression risk, and clinical symptoms, and they suggest a means of readily identifying a subset of patients with an active inflammatory state and worse prognosis.

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Modulation of CD14 and TLR4⋅MD‐2 Activities by a Synthetic Lipid A Mimetic

et al. 2013

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Monosaccharide lipid A mimetics composed by a glucosamine core linked to two fatty acid chains and bearing one or two phosphates have been synthesized. While compounds 1 and 2, with one phosphate group, were practically inactive in inhibiting LPS-induced TLR4 signaling and cytokine production in HEK-blue™ cells and murine macrophages, compound 3 with two phosphates was found to be active in efficiently inhibiting TLR4 signal in both cell types. The direct interaction of molecule 3 with MD-2 co-receptor has been investigated by means of NMR and molecular modeling/docking analysis. This compound also interacts directly with CD14 receptor, stimulating its internalization by endocytosis. Experiments on macrophages show that the effect on CD14 reinforces the activity on MD-2.TLR4, because compound 3 activity is higher when CD14 is important for TLR4 signaling i,e, at low LPS concentration. The dual MD-2 and CD14 targeting, accompanied by good solubility in water and lack of toxicity, suggests the use of monosaccharide 3 as a lead compound to develop drugs directed against TLR4-related syndromes.

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The contributing role of CD14 in toll-like receptor 4 dependent neuropathic pain

Cited by 95 publications

References 39 publications

Evaluating the role of Toll-like receptors in diseases of the central nervous system

Evaluating the role of Toll-like receptors in diseases of the central nervous system

Soluble Macrophage Biomarkers Indicate Inflammatory Phenotypes in Patients With Knee Osteoarthritis

Modulation of CD14 and TLR4⋅MD‐2 Activities by a Synthetic Lipid A Mimetic

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