Comparison of PPAR Ligands as Modulators of Resolution of Inflammation, via Their Influence on Cytokines and Oxylipins Release in Astrocytes

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

doi:10.3390/ijms21249577

Cited by 24 publications

(17 citation statements)

References 73 publications

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“…To identify the difference between lipid fractions, we analyzed them using the approach we developed previously with the mass-spectrometric method of oxylipin profiles detection [ 35 , 36 ]. We obtained oxylipin profiles from astrocytes treated solely with LPS, ML355, and Zileuton or in combinations for 24 h ( Figure 4 A).…”

Section: Resultsmentioning

confidence: 99%

Modulation of the Primary Astrocyte-Enriched Cultures’ Oxylipin Profiles Reduces Neurotoxicity

et al. 2021

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Recently, manipulations with reactive astrocytes have been viewed as a new therapeutic approach that will enable the development of treatments for acute brain injuries and neurodegenerative diseases. Astrocytes can release several substances, which may exert neurotoxic or neuroprotective effects, but the nature of these substances is still largely unknown. In the present work, we tested the hypothesis that these effects may be attributed to oxylipins, which are synthesized from n-3 or n-6 polyunsaturated fatty acids (PUFAs). We used astrocyte-enriched cultures and found that: (1) lipid fractions secreted by lipopolysaccharide (LPS)—stimulated rat primary astrocyte-enriched cultures—possessed neurotoxic activity in rat primary neuronal cultures; (2) both of the tested oxylipin synthesis inhibitors, ML355 and Zileuton, reduce the LPS-stimulated release of interleukin 6 (IL-6) by astrocyte cultures, but only ML355 can change lipid fractions from neurotoxic to non-toxic; and (3) oxylipin profiles, measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) from neurotoxic and non-toxic lipid fractions, reveal a group of n-3 docosahexaenoic acid derivatives, hydroxydocosahexaenoic acids (HdoHEs)-4-HdoHE, 8-HdoHE, and 17-HdoHE, which may reflect the neuroprotective features of lipid fractions. Regulating the composition of astrocyte oxylipin profiles may be suggested as an approach for regulation of neurotoxicity in inflammatory processes.

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Section: Resultsmentioning

confidence: 99%

Modulation of the Primary Astrocyte-Enriched Cultures’ Oxylipin Profiles Reduces Neurotoxicity

et al. 2021

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“…There is evidence that treatment with the ligand (WY14643) of peroxisome-proliferator-activated receptor alpha facilitates the expression of anti-inflammatory cytokine interleukin-10 mRNA in rats [ 67 ]. The peroxisome-proliferator-activated receptor beta agonist (GW501516) and the peroxisome-proliferator-activated receptor gamma agonist (rosiglitazone) elicit the interleukin-10 release [ 68 ]. Besides upregulating M2 polarization-related factor interleukin-10, the use of peroxisome-proliferator-activated receptor gamma agonists also can downregulate macrophage M1 polarization-related factors such as interleukin-1 and interleukin-6 [ 69 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison and Analysis on the Existing Single-Herbal Strategies against Viral Myocarditis

et al. 2021

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Purpose. Herbal medicine is one of crucial symbols of Chinese national medicine. Investigation on molecular responses of different herbal strategies against viral myocarditis is immeasurably conducive to targeting drug development in the current international absence of miracle treatment. Methods. Literature retrieval platforms were applied in the collection of existing empirical evidences for viral myocarditis-related single-herbal strategies. SwissTargetPrediction, Metascape, and Discovery Studio coordinating with multidatabases investigated underlying target genes, interactive proteins, and docking molecules in turn. Results. Six single-herbal medicines consisting of Huangqi (Hedysarum Multijugum Maxim), Yuganzi (Phyllanthi Fructus), Kushen (Sophorae Flavescentis Radix), Jianghuang (Curcumaelongae Rhizoma), Chaihu (Radix Bupleuri), and Jixueteng (Spatholobus Suberectus Dunn) meet the requirement. There were 11 overlapped and 73 unique natural components detected in these herbs. SLC6A2, SLC6A4, NOS2, PPARA, PPARG, ACHE, CYP2C19, CYP51A1, and CHRM2 were equally targeted by six herbs and identified as viral myocarditis-associated symbols. MCODE algorithm exposed the hub role of SRC and EGFR in strategies without Jianghuang. Subsequently, we learned intermolecular interactions of herbal components and their targeting heart-tissue-specific CHRM2, FABP3, TNNC1, TNNI3, TNNT2, and SCN5A and cardiac-myocytes-specific IL6, MMP1, and PLAT coupled with viral myocarditis. Ten interactive characteristics such as π-alkyl and van der Waals were modeled in which ARG111, LYS253, ILE114, and VAL11 on cardiac troponin (TNNC1-TNNI3-TNNT2) and ARG208, ASN106, and ALA258 on MMP1 fulfilled potential communicating anchor with ellagic acid, 5α, 9α-dihydroxymatrine, and leachianone g via hydrogen bond and hydrophobic interaction, respectively. Conclusions. The comprehensive outcomes uncover differences and linkages between six herbs against viral myocarditis through component and target analysis, fostering development of drugs.

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“…Rice bran extract (which is rich in PUFA) as well as pioglitazone have been reported to protect against inflammation induced by lipopolysaccharides (LPS) in a mouse model, decreasing TNF-a and COX2 levels in brain, reducing striatal plaque formation and suppressing cortical and hippocampal tissue damage, all effects requiring PPARγ activity [60]. Other recent studies converged to support positive, PPARγ-dependent, role against neuroinflammation of PPARγ agonists as rosiglitazone which induced IL-10 in primary rat astrocytes exposed to LPS [61], or pioglitazone in a rat model of chronic intermittent hypoxia [62]. Other studies did not assess PPARγ involvement but still reported a protective role of its agonists against neuroinflammation, as rosiglitazone in a mouse model of epilepsy [63] and pioglitazone in rat models of autism [64], Parkinson's disease [65], or neuroinflammation due to intracerebroventricular administration of LPS [66].…”

Section: Neuroinflammationmentioning

confidence: 99%

PPAR Gamma and Viral Infections of the Brain

Layrolle

Payoux

Chavanas

2021

IJMS

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Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a master regulator of metabolism, adipogenesis, inflammation and cell cycle, and it has been extensively studied in the brain in relation to inflammation or neurodegeneration. Little is known however about its role in viral infections of the brain parenchyma, although they represent the most frequent cause of encephalitis and are a major threat for the developing brain. Specific to viral infections is the ability to subvert signaling pathways of the host cell to ensure virus replication and spreading, as deleterious as the consequences may be for the host. In this respect, the pleiotropic role of PPARγ makes it a critical target of infection. This review aims to provide an update on the role of PPARγ in viral infections of the brain. Recent studies have highlighted the involvement of PPARγ in brain or neural cells infected by immunodeficiency virus 1, Zika virus, or human cytomegalovirus. They have provided a better understanding on PPARγ functions in the infected brain, and revealed that it can be a double-edged sword with respect to inflammation, viral replication, or neuronogenesis. They unraveled new roles of PPARγ in health and disease and could possibly help designing new therapeutic strategies.

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Comparison of PPAR Ligands as Modulators of Resolution of Inflammation, via Their Influence on Cytokines and Oxylipins Release in Astrocytes

Cited by 24 publications

References 73 publications

Modulation of the Primary Astrocyte-Enriched Cultures’ Oxylipin Profiles Reduces Neurotoxicity

Modulation of the Primary Astrocyte-Enriched Cultures’ Oxylipin Profiles Reduces Neurotoxicity

Comparison and Analysis on the Existing Single-Herbal Strategies against Viral Myocarditis

PPAR Gamma and Viral Infections of the Brain

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