High and Low Molecular Weight Hyaluronic Acid Differentially Influences Oxylipins Synthesis in Course of Neuroinflammation

Chistyakov, Dmitry V.; Astakhova, A. A.; Azbukina, Nadezhda V.; Goriainov, Sergei V.; Chistyakov, V. V.; Sergeeva, Marina G.

doi:10.3390/ijms20163894

Cited by 49 publications

(51 citation statements)

References 41 publications

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“…Oxylipins are lipid-signaling molecules produced by multiple enzymatic reactions and are derived from the oxidation of PUFAs [5]. The recent development of mass spectrometry has enabled the analysis of oxylipin profiles [5,27]. To characterize whether cultured astrocytes adapted for various cytokines or LPS possess various abilities for oxylipin synthesis, we compared the oxylipin profiles in rat astrocyte cultures following long-term exposure to LPS (100 ng/mL), IL-4 (10 ng/mL), IL-10 (20 ng/mL), and low-concentration LPS (ET, 10 ng/mL).…”

Section: Oxylipin Profiles Of Astrocytes With Different Adaptation Stmentioning

confidence: 99%

“…Mechanisms of these changes and the possibilities of directed regulation are unexplored. Although we characterized astrocyte oxylipin synthesis for pro-inflammatory stimuli [20,26,27], the data concerning oxylipin synthesis in various astrocyte polarization states are missing. Therefore, we stimulated astrocytes with interleukin 4 (IL-4), interleukin 10 (IL-10), and LPS for 24 h (h) and subdivided their phenotypic polarization into A1-like (pro-inflammatory, classical) and A2-like (anti-inflammatory, alternative) using the previously suggested markers [23,28].…”

Section: Introductionmentioning

confidence: 99%

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Oxylipin Profiles as Functional Characteristics of Acute Inflammatory Responses in Astrocytes Pre-Treated with IL-4, IL-10, or LPS

Chistyakov

Gavrish

Goriainov

et al. 2020

IJMS

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Functional phenotypes, which cells can acquire depending on the microenvironment, are currently the focus of investigations into new anti-inflammatory therapeutic approaches. Glial cells, microglia, and astrocytes are major participants in neuroinflammation, but their roles differ, as microglia are cells of mesodermal origin, while astrocytes are cells of ectodermal origin. The inflammatory phenotype of cells can be modulated by ω-6- and ω-3-polyunsaturated fatty acid-derived oxylipins, although data on changes in oxylipin profiles in different cell adaptations to pro- and anti-inflammatory stimuli are scarce. Our study aimed to compare UPLC-MS/MS-measured oxylipin profiles in various rat astrocyte adaptation states. We used cells treated for 24 h with lipopolysaccharide (LPS) for classical pro-inflammatory adaptation and with interleukin 4 (IL-4) or 10 (IL-10) for alternative anti-inflammatory adaptation, with the resulting phenotypes characterized by quantitative real-time PCR (RT-PCR). We also tested long-term, low-concentration LPS treatment (endotoxin treatment) as a model of astrocyte adaptations. The functional response of astrocytes was estimated by acute (4 h) LPS-induced cell reactivity, measured by gene expression markers and oxylipin synthesis. We discovered that, as well as gene markers, oxylipin profiles can serve as markers of pro- (A1-like) or anti-inflammatory (A2-like) adaptations. We observed predominant involvement of ω-6 polyunsaturated fatty acid (PUFA) and the cyclooxygenase branch for classical (LPS) pro-inflammatory adaptations and ω-3 PUFA and the lipoxygenase branch for alternative (IL-4) anti-inflammatory adaptations. Treatment with IL-4, but not IL-10, primes the ability of astrocytes to activate the innate immunity signaling pathways in response to LPS. Endotoxin-treated astrocytes provide an alternative anti-inflammatory adaptation, which makes cells less sensitive to acute LPS stimulation than the IL-4 induced adaptation. Taken together, the data reveal that oxylipin profiles associate with different states of polarization to generate a pro-inflammatory or anti-inflammatory phenotype. This association manifests itself both in native cells and in their responses to a pro-inflammatory stimulus.

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Section: Oxylipin Profiles Of Astrocytes With Different Adaptation Stmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oxylipin Profiles as Functional Characteristics of Acute Inflammatory Responses in Astrocytes Pre-Treated with IL-4, IL-10, or LPS

Chistyakov

Gavrish

Goriainov

et al. 2020

IJMS

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“…The cell-free culture media were taken for the solid-phase lipid extraction (Oasis ® PRIME HLB cartridge (60 mg, 3cc)) as described before [23]. For identification of lipid mediators, the respective lipid extracts were analyzed using 8040 series UPLC-MS/MS mass spectrometer (Shimadzu, Japan) in multiple-reaction monitoring mode at a unit mass resolution for both the precursor and product ions [23]. Comprehensive analysis of lipid metabolites was performed by using a composition of internal standards (tetranor-PGEM-d6 (cat.no.…”

Section: Uplc-ms/ms Conditions and Sample Preparationmentioning

confidence: 99%

Cellular Model of Endotoxin Tolerance in Astrocytes: Role of Interleukin 10 and Oxylipins

Chistyakov

Astakhova

Azbukina

et al. 2019

Cells

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A phenomenon of endotoxin tolerance where prior exposure of cells to minute amounts of lipopolysaccharide (LPS) causes them to become refractory to a subsequent high-amount endotoxin challenge is well described for innate immune cells such as monocytes/macrophages, but it is still obscure for brain cells. We exposed primary rat cortical astrocytes to a long-term low-grade concentration of LPS, followed by stimulation with a middle-grade concentration of LPS. Inflammatory markers, i.e., pro-inflammatory cytokine TNFα, inducible enzymes COX-2 and iNOS, anti-inflammatory cytokine interleukin 10 (IL-10) detected at the mRNA and protein levels reveal similarities between astrocytes and macrophages in the model, i.e., tolerance in pro-inflammatory markers and priming in IL-10. Long-term or short-term treatment with IL-10 does not change cell sensitivity for LPS, which makes doubtful its involvement in the mechanisms of cell tolerance development. Significant changes occur in the oxylipin profiles measured by UPLC-MS/MS analysis. The priming occurs in the following compounds: 11-HETE, PGD 2 , PGE 2 , cyclopentenone prostaglandins, and TXB 2 . Tolerance is observed for 12-HHT, PGF 2α , and 6-keto-PGF 1α . As far as we know, this is the first report on changes in oxylipin profiles in the endotoxin tolerance model. The data can greatly improve the understanding of oxylipins' role in inflammatory and resolution processes in the brain and mechanisms of astrocyte involvement in neuroinflammation.

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“…Initially, we retained the reaction components: HA, PEG‐NH 2 , and EDC/NHS and manipulated molar equivalents, the sequence of addition, reaction time, buffer and pH to improve efficiency. Anti‐inflammatory properties of high molecular weight HA (1 MDa) prompted its choice as the base polymer [ 34,35 ] for cross‐linking with PEG‐NH 2 (2000 Da). EDC was an obvious choice as carbodiimide owing to the water solubility of its urea bi‐product.…”

Section: Resultsmentioning

confidence: 99%

Crossing the hurdles of translation—a robust methodology for synthesis, characterization and GMP production of cross‐linked high molecular weight hyaluronic acid particles (cHA)

et al. 2020

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Hyaluronic acid (HA) is one of the most widely used extracellular matrix substrate in tissue engineering, drug delivery, and other clinical applications, due to its unique physiochemical properties and ubiquitous biological presence. In the past decade, there has been a surge in research paradigms involving HA products to evaluate their commercial feasibility. Numerous papers and reviews have reported procedures for chemical modifications and cross‐linking of HA, but the intricacies of their scale‐up in the production processes are often not discussed. Protected by confidentiality agreements with industry partners, information on these procedures is exclusive and not accessible within an academic setting. Establishing translatable synthetic protocols of HA would address this significant gap in the field and facilitate their use in other applications. The current method details a reproducible and robust method for producing particles that are composed of high molecular weight hyaluronic acid (cHA) and cross‐linked via a 4‐arm polyethylene glycol amine linker using 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methyl‐morpholinium chloride chemistry. A critical analysis of previously reported procedures for their advantages and limitations (reaction parameters, molar equivalents, and reagents used for cross‐linking), forms the basis for this procedure and its subsequent adaptation to good manufacturing practices requirements. As a component of a Class III medical device, the reported cHA is in the form of non‐sized particles.

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High and Low Molecular Weight Hyaluronic Acid Differentially Influences Oxylipins Synthesis in Course of Neuroinflammation

Cited by 49 publications

References 41 publications

Oxylipin Profiles as Functional Characteristics of Acute Inflammatory Responses in Astrocytes Pre-Treated with IL-4, IL-10, or LPS

Oxylipin Profiles as Functional Characteristics of Acute Inflammatory Responses in Astrocytes Pre-Treated with IL-4, IL-10, or LPS

Cellular Model of Endotoxin Tolerance in Astrocytes: Role of Interleukin 10 and Oxylipins

Crossing the hurdles of translation—a robust methodology for synthesis, characterization and GMP production of cross‐linked high molecular weight hyaluronic acid particles (cHA)

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