Current status and relevance of single nucleotide polymorphisms in IL-6-/IL-12-type cytokine receptors

Scheller, Jürgen; Berg, Anna F.; Moll, Jens M.; Floß, Doreen M.; Jungesblut, Christopher

doi:10.1016/j.cyto.2021.155550

Cited by 9 publications

(6 citation statements)

References 95 publications

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“…A highly specific distribution of receptors was first noted for IL-1 ( Farrar et al, 1987 ) but has since been described for many others ( Cayrol and Girard, 2022 ) with receptors located on different cells or groups ( Gour and Wills-Karp, 2015 ; Hurdayal and Brombacher, 2017 ; Johnston and Bryce, 2017 ; Fairlie-Clarke et al, 2018 ; Younger et al, 2019 ; Wilson, 2021 ). In contrast, cytokines are often produced by distinct populations of cells, giving the compounds marked differences in kinetics and regional specificity ( Scheller et al, 2021 ; Evavold and Kagan, 2022 ).…”

Section: An Integrated Kynurenine-cytokine Systemmentioning

confidence: 99%

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

et al. 2022

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Two of the molecular families closely associated with mediating communication between the brain and immune system are cytokines and the kynurenine metabolites of tryptophan. Both groups regulate neuron and glial activity in the central nervous system (CNS) and leukocyte function in the immune system, although neither group alone completely explains neuroimmune function, disease occurrence or severity. This essay suggests that the two families perform complementary functions generating an integrated network. The kynurenine pathway determines overall neuronal excitability and plasticity by modulating glutamate receptors and GPR35 activity across the CNS, and regulates general features of immune cell status, surveillance and tolerance which often involves the Aryl Hydrocarbon Receptor (AHR). Equally, cytokines and chemokines define and regulate specific populations of neurons, glia or immune system leukocytes, generating more specific responses within restricted CNS regions or leukocyte populations. In addition, as there is a much larger variety of these compounds, their homing properties enable the superimposition of dynamic variations of cell activity upon local, spatially limited, cell populations. This would in principle allow the targeting of potential treatments to restricted regions of the CNS. The proposed synergistic interface of ‘tonic’ kynurenine pathway affecting baseline activity and the superimposed ‘phasic’ cytokine system would constitute an integrated network explaining some features of neuroimmune communication. The concept would broaden the scope for the development of new treatments for disorders involving both the CNS and immune systems, with safer and more effective agents targeted to specific CNS regions.

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Section: An Integrated Kynurenine-cytokine Systemmentioning

confidence: 99%

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

et al. 2022

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“…Secondly, although gp130 (IL-6Rβ) is an essential part of the IL-6R and its inhibition blocks signal transduction, it also participates in the signaling of other members of the IL-6/IL-12 family (e.g., IL-11, IL-23 and IL-35) [57]. The binding of both bis-pentamethinium salts to gp130 thus implies they not only block IL-6 signaling.…”

Section: Influence Of Bis-pentamethinium Salts 5 and 6 On Mitochondri...mentioning

confidence: 99%

New-Generation Heterocyclic Bis-Pentamethinium Salts as Potential Cytostatic Drugs with Dual IL-6R and Mitochondria-Targeting Activity

et al. 2022

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IL-6 signaling is involved in the pathogenesis of a number of serious diseases, including chronic inflammation and cancer. Targeting of IL-6 receptor (IL-6R) by small molecules is therefore an intensively studied strategy in cancer treatment. We describe the design, synthesis, and characteristics of two new bis-pentamethinium salts 5 and 6 (meta and para) bearing indole moieties. Molecular docking studies showed that both compounds have the potential to bind IL-6R (free energy of binding −9.5 and −8.1 kcal/mol). The interaction with IL-6R was confirmed using microscale thermophoresis analyses, which revealed that both compounds had strong affinity for the IL-6R (experimentally determined dissociation constants 26.5 ± 2.5 nM and 304 ± 27.6 nM, respectively). In addition, both compounds were cytotoxic for a broad spectrum of cancer cell lines in micromolar concentrations, most likely due to their accumulation in mitochondria and inhibition of mitochondrial respiration. In summary, the structure motif of bis-pentamethinium salts represents a promising starting point for the design of novel multitargeting compounds with the potential to inhibit IL-6 signaling and simultaneously target mitochondrial metabolism in cancer cells.

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“…In addition to the proliferative effects of GM-CSF on alveolar macrophages (AMs), GM-CSF increases the AMs phagocytic capacity, as well as accelerates the division of lung dendritic cells (DCs) that accumulate during TB [17,18]. The results of limited studies conducted have shown that single nucleotide polymorphism (SNP) in IL-23R is associated with susceptible to tuberculosis (TB) disease [19,20]. So far, no study in relation to single nucleotide polymorphism located in the GM-CSF gene susceptible to tuberculosis (TB) disease has been performed.…”

Section: Tuberculosis Is An Intracellular Bacterialmentioning

confidence: 99%

The relationship between IL23R 1142G / A (Arg381Gln) and GM-CSF 3928 C / T (Ile117Thr) gene polymorphism in Iranian patients with tuberculosis disease

Kahkhaie

Keikhaie

Rezaie-Kahkhaie

et al. 2021

Cell. Mol. Biomed. Rep.

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The DNA polymorphisms found in clinical strains of Mycobacterium tuberculosis drive altered physiology, virulence, and pathogenesis in them. This study aimed to investigate the association between IL23R 1142 G/A (Arg381Gln) and GM-CSF 3928 C/T (Ile117Thr) gene polymorphisms with the incidence rate of tuberculosis in the population of Sistan. This study was based on the descriptive and applied type. All patients with active pulmonary tuberculosis were referred to the tuberculosis center of Zabol city for one year, with an equal number of healthy people adapted to the patients examined in terms of age. After data collecting to compare the frequency of polymorphisms, the chisquare test and OR index were used using SPSS software version 16. We have found that the IL23R reduced-function allele 1142A and genotypes CC and TC were overrepresented, especially in the Pad subgroup compared with the control group (44% versus 42%, 21% versus 22%, and 44% versus 39%, respectively. Increased risks of TB with minimal/moderate lung involvement, respectively. Our results demonstrate that the reduced-function polymorphism 1142G ¡ A encoded by IL23R influences the outcome of disease severity of active pulmonary TB in ZABOL patients. The genotypic and allelic frequency of IL23R 1142 G/A, and GM-CSF 3928 C/T (Ile117Thr) polymorphism in patients with tuberculosis was significantly different from the control group and this polymorphism was associated with the incidence of tuberculosis in the population of Sistan.

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Current status and relevance of single nucleotide polymorphisms in IL-6-/IL-12-type cytokine receptors

Cited by 9 publications

References 95 publications

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

New-Generation Heterocyclic Bis-Pentamethinium Salts as Potential Cytostatic Drugs with Dual IL-6R and Mitochondria-Targeting Activity

The relationship between IL23R 1142G / A (Arg381Gln) and GM-CSF 3928 C / T (Ile117Thr) gene polymorphism in Iranian patients with tuberculosis disease

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