Regulation of Chemokine–Receptor Interactions and Functions

Stone, Martin J.

doi:10.3390/ijms18112415

Cited by 21 publications

(20 citation statements)

References 17 publications

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“…The acute inflammation is an initial response, which is characterized by resident cell activation, with liberation of proinflammatory cytokines and chemokines, culminating in the recruitment of polymorphonuclear, primarily neutrophils, from the innate immune system to the injury site. This response complex act to promote cardinal signs of inflammation, such as pain, edema, and heat [ 19 ]. On the other hand, chronic inflammation is a prolonged response characterized by a gradual change in the cells type found at the inflammatory site, which over time cause both permanent damage and healing of the tissue.…”

Section: Introductionmentioning

confidence: 99%

An Overview on the Anti‐inflammatory Potential and Antioxidant Profile of Eugenol

Barboza

Filho

Silva

et al. 2018

Oxidative Medicine and Cellular Longevity

215

155

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The bioactive compounds found in foods and medicinal plants are attractive molecules for the development of new drugs with action against several diseases, such as those associated with inflammatory processes, which are commonly related to oxidative stress. Many of these compounds have an appreciable inhibitory effect on oxidative stress and inflammatory response, and may contribute in a preventive way to improve the quality of life through the use of a diet rich in these compounds. Eugenol is a natural compound that has several pharmacological activities, action on the redox status, and applications in the food and pharmaceutical industry. Considering the importance of this compound, the present review discusses its anti-inflammatory and antioxidant properties, demonstrating its mechanisms of action and therapeutic potential for the treatment of inflammatory diseases.

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Section: Introductionmentioning

confidence: 99%

An Overview on the Anti‐inflammatory Potential and Antioxidant Profile of Eugenol

Barboza

Filho

Silva

et al. 2018

Oxidative Medicine and Cellular Longevity

215

155

View full text Add to dashboard Cite

show abstract

“…The lack of success in trials of anti-inflammatory drugs targeting chemokine receptors can be attributed in part to the complex regulation of chemokine–receptor networks. These networks can be regulated on numerous levels, including gene expression, alternative splicing, partial proteolysis, various other post-translational modifications, control of stability or localization, and competition with active or decoy receptors [18,19]. Moreover, it is now well established that, like other GPCRs, chemokine receptors are able to stimulate different intracellular signaling pathways (and therefore cellular outcomes) when activated by different chemokine ligands, a phenomenon known as biased agonism.…”

Section: Introductionmentioning

confidence: 99%

Influence of Chemokine N-Terminal Modification on Biased Agonism at the Chemokine Receptor CCR1

Lane

Canals

Stone

2019

IJMS

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Leukocyte migration, a hallmark of the inflammatory response, is stimulated by the interactions between chemokines, which are expressed in injured or infected tissues, and chemokine receptors, which are G protein-coupled receptors (GPCRs) expressed in the leukocyte plasma membrane. One mechanism for the regulation of chemokine receptor signaling is biased agonism, the ability of different chemokine ligands to preferentially activate different intracellular signaling pathways via the same receptor. To identify features of chemokines that give rise to biased agonism, we studied the activation of the receptor CCR1 by the chemokines CCL7, CCL8, and CCL15(Δ26). We found that, compared to CCL15(Δ26), CCL7 and CCL8 exhibited biased agonism towards cAMP inhibition and away from β-Arrestin 2 recruitment. Moreover, N-terminal substitution of the CCL15(Δ26) N-terminus with that of CCL7 resulted in a chimera with similar biased agonism to CCL7. Similarly, N-terminal truncation of CCL15(Δ26) also resulted in signaling bias between cAMP inhibition and β-Arrestin 2 recruitment signals. These results show that the interactions of the chemokine N-terminal region with the receptor transmembrane region play a key role in selecting receptor conformations coupled to specific signaling pathways.

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“…A unique feature of chemokines has been commonly demonstrated to be the nature of receptors to which they bind. Chemokines have been shown to elicit their effects mainly by activating specific transmembrane receptors which belong to the large family of G protein-coupled receptors (GPCRs) [16]. The receptor of CCL18 involved in mediating tumour pathogenesis has been investigated in many cancers; however, the specific receptor of CCL18 in oral cancer remains uncertain.…”

Section: Discussionmentioning

confidence: 99%

CCL18-NIR1/GPR3 promotes oral cancer cell growth and metastasis by activating the JAK2/STAT3 signalling pathway

Chen

Jiang

Sun

et al. 2019

Preprint

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Background Chemokine (C-C motif) ligand 18 (CCL18) affects the malignant progression of varying cancers by activating chemokine receptors. Our previous study have shown that CCL18 promotes hyperplasia and invasiveness of oral cancer cells; however, the cognate receptors of CCL18 involved in the pathogenesis of oral squamous cell carcinoma (OSCC) has not yet been identified. This study aimed to investigate the underlying molecular mechanisms through which CCL18 promotes OSCC progression by binding to specific functional receptors.Methods The properties of CCL18 receptors (i.e., NIR1, CCR6, CCR8, and GPR3) in OSCC were detected by conducting western blotting, immunofluorescence, and immunocytochemistry assays. The binding between CCL18 and its receptors was verified by performing coimmunoprecipitation (CO-IP) assays. The χ2 test was applied to analyze the relationship between CCL18 receptor expression patterns and clinicopathological factors. Recombinant CCL18 (rCCL18) and receptor siRNA were used to confirm the effects of CCL18 receptor axis on the morphology of cancer cells (i.e., proliferation, and metastasis), epithelial-mesenchymal transition (EMT) and the expression of the JAK2/STAT3 signalling pathway.Results NIR1 and GPR3 as specific receptors of CCL18 in OSCC were found to be significantly increased and positively related to the TNM stage of OSCC patients. rCCL18 induced phenotype alterations of oral cancer cells including cell growth, metastasis, and EMT. Knockdown of NIR1 and/or GPR3 expression could block the effects of rCCL18-induced OSCC. Furthermore, JAK2/STAT3 signalling was confirmed to be a downstream pathway of the CCL18-NIR1/GPR3 axis.Conclusion CCL18 can promote the progression of OSCC by binding specific receptors (NIR1 and GPR3), and the CCL18-receptor signalling can activate JAK2/STAT3 pathway. The identification of the mechanisms of CCL18 promoting OSCC progression could implicate potential therapeutic targets for treating oral cancer.

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Regulation of Chemokine–Receptor Interactions and Functions

Abstract: Inflammation is the body’s response to injury or infection. As early as 2000 years ago, the Roman encyclopaedist Aulus Cornelius Celsus recognised four cardinal signs of this response—redness, heat, swelling and pain; a fifth sign is loss of function.[...]

Cited by 21 publications

References 17 publications

An Overview on the Anti‐inflammatory Potential and Antioxidant Profile of Eugenol

An Overview on the Anti‐inflammatory Potential and Antioxidant Profile of Eugenol

Influence of Chemokine N-Terminal Modification on Biased Agonism at the Chemokine Receptor CCR1

CCL18-NIR1/GPR3 promotes oral cancer cell growth and metastasis by activating the JAK2/STAT3 signalling pathway

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