scholarly journals Early-Released Interleukin-10 Significantly Inhibits Lipopolysaccharide-Elicited Neuroinflammation In Vitro

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2173
Author(s):  
Yubao Wang ◽  
Pei Yu ◽  
Yi Li ◽  
Zhan Zhao ◽  
Xiaomei Wu ◽  
...  
Keyword(s):  
Late Phase ◽  
Interleukin 10 ◽  
Glial Cultures ◽  
Pilot Investigation ◽  
The Central Nervous System ◽  
Β2 Adrenergic Receptor ◽  
Anti Inflammatory ◽  
Protein Assays

Anti-inflammatory cytokine interleukin (IL)-10 is pivotal for limiting excessive inflammation in the central nervous system. Reports show that lipopolysaccharide (LPS)-induced microglial IL-10 emerges in a delayed manner in vitro and in vivo, lagging behind proinflammatory cytokines to facilitate the resolution of neuroinflammation. We hypothesized that IL-10 releases quite quickly based on our pilot investigation. Here, we uncovered a bimodal expression of microglial IL-10 gene transcription induced by LPS in mouse primary mixed glial cultures. This pattern consisted of a short brief early-phase and a long-lived late-phase, enabling the production of IL-10 protein in a rapid manner. The removal and addition of IL-10 protein assays indicated that early-released IL-10 exerted potent modulatory effects on neuroinflammation at picomolar levels, and IL-10 released at the onset of neuroinflammation is tightly controlled. We further showed that the early-released, but not the late-released, IL-10 was crucial for mediating and potentiating the anti-inflammatory function of a β2-adrenergic receptor agonist salmeterol. This study in vitro highlights the essential role of early-released IL-10 in regulating the appropriate degree of neuroinflammation, overturning the previous notion that microglial IL-10 produces and functions in a delayed manner and providing new insights into anti-inflammatory mechanisms-mediated neuroimmune homeostasis.

scholarly journals Dual Role of Interleukin-10 in Murine NZB/W F1 Lupus

2021 ◽  
Vol 22 (3) ◽  
pp. 1347
Author(s):  
Anaïs Amend ◽  
Natalie Wickli ◽  
Anna-Lena Schäfer ◽  
Dalina T. L. Sprenger ◽  
Rudolf A. Manz ◽  
...  
Keyword(s):  
B Cell ◽  
Disease Model ◽  
Interleukin 10 ◽  
Immune Functions ◽  
Murine Lupus ◽  
Anti Inflammatory ◽  
In Vivo Effects

As a key anti-inflammatory cytokine, IL-10 is crucial in preventing inflammatory and autoimmune diseases. However, in human and murine lupus, its role remains controversial. Our aim was to understand regulation and immunologic effects of IL-10 on different immune functions in the setting of lupus. This was explored in lupus-prone NZB/W F1 mice in vitro and vivo to understand IL-10 effects on individual immune cells as well as in the complex in vivo setting. We found pleiotropic IL-10 expression that largely increased with progressing lupus, while IL-10 receptor (IL-10R) levels remained relatively stable. In vitro experiments revealed pro- and anti-inflammatory IL-10 effects. Particularly, IL-10 decreased pro-inflammatory cytokines and slowed B cell proliferation, thereby triggering plasma cell differentiation. The frequent co-expression of ICOS, IL-21 and cMAF suggests that IL-10-producing CD4 T cells are important B cell helpers in this context. In vitro and in vivo effects of IL-10 were not fully concordant. In vivo IL-10R blockade slightly accelerated clinical lupus manifestations and immune dysregulation. Altogether, our side-by-side in vitro and in vivo comparison of the influence of IL-10 on different aspects of immunity shows that IL-10 has dual effects. Our results further reveal that the overall outcome may depend on the interplay of different factors such as target cell, inflammatory and stimulatory microenvironment, disease model and state. A comprehensive understanding of such influences is important to exploit IL-10 as a therapeutic target.

scholarly journals In Vivo and In Vitro Toxicodynamic Analyses of New Quinolone-and Nonsteroidal Anti-Inflammatory Drug-Induced Effects on the Central Nervous System

1999 ◽  
Vol 43 (5) ◽  
pp. 1091-1097 ◽  
Author(s):  
Hideki Kita ◽  
Hirotami Matsuo ◽  
Hitomi Takanaga ◽  
Junichi Kawakami ◽  
Koujirou Yamamoto ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Threshold Concentration ◽  
Current Response ◽  
Drug Induced ◽  
Inhibition Ratio ◽  
New Quinolones ◽  
The Central Nervous System ◽  
Anti Inflammatory

ABSTRACT We investigated the correlation between an in vivo isobologram based on the concentrations of new quinolones (NQs) in brain tissue and the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) for the occurrence of convulsions in mice and an in vitro isobologram based on the concentrations of both drugs for changes in the γ-aminobutyric acid (GABA)-induced current response in Xenopus oocytes injected with mRNA from mouse brains in the presence of NQs and/or NSAIDs. After the administration of enoxacin (ENX) in the presence or absence of felbinac (FLB), ketoprofen (KTP), or flurbiprofen (FRP), a synergistic effect was observed in the isobologram based on the threshold concentration in brain tissue between mice with convulsions and those without convulsions. The three NSAIDs did not affect the pharmacokinetic behavior of ENX in the brain. However, the ENX-induced inhibition of the GABA response in the GABAA receptor expressed in Xenopus oocytes was enhanced in the presence of the three NSAIDs. The inhibition ratio profiles of the GABA responses for both drugs were analyzed with a newly developed toxicodynamic model. The inhibitory profiles for ENX in the presence of NSAIDs followed the order KTP (1.2 μM) > FRP (0.3 μM) > FLB (0.2 μM). These were 50- to 280-fold smaller than those observed in the absence of NSAIDs. The inhibition ratio (0.01 to 0.02) of the GABAA receptor in the presence of both drugs was well-fitted to the isobologram based on threshold concentrations of both drugs in brain tissue between mice with convulsions and those without convulsions, despite the presence of NSAIDs. In mice with convulsions, the inhibitory profiles of the threshold concentrations of both drugs in brain tissue of mice with convulsions and those without convulsions can be predicted quantitatively by using in vitro GABA response data and toxicodynamic model.

scholarly journals Mesenchymal Stem Cell Therapy Ameliorates Metabolic Dysfunction and Restores Fertility in a PCOS Mouse Model Through Interleukin-10

2021 ◽  
Author(s):  
Rishi Man Chugh ◽  
Hang-soo Park ◽  
Abdeljabar El Andaloussi ◽  
Amro Elsharoud ◽  
Sahar Esfandyari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polycystic Ovary ◽  
Therapeutic Option ◽  
Interleukin 10 ◽  
Reproductive Age ◽  
Metabolic Dysfunction ◽  
Mesenchymal Stem Cell Therapy ◽  
Anti Inflammatory

Abstract Background: Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-age women. Excessive inflammation and elevated androgen production from ovarian theca cells are key features of PCOS. Human bone marrow mesenchymal stem cells (BM-hMSC) and their secreted factors (secretome) exhibit robust anti-inflammatory capabilities in various biological systems. We evaluated the therapeutic efficacy of BM-hMSC and its secretome in both in vitro and in vivo PCOS models.Methods: For in vitro experiment, we treated conditioned media from BM-hMSC to androgen producing H293R cells, and analyzed androgen producing gene expression. For in vivo experiment, BM-hMSC were implanted into Letrozole (LTZ) induced mouse PCOS model. BM-hMSC effect in androgen producing cells or PCOS model mice was assessed by monitoring cell proliferation (immunohistochemistry), steroidogenic gene expression (quantitative real-time polymerase chain reaction [qRT-PCR] and Western blot, animal tissue assay (H&E staining), and fertility by pup delivery.Results: BM-hMSC significantly downregulate steroidogenic gene expression, curb inflammation, and restore fertility in treated PCOS animals. The anti-inflammatory cytokine interleukin-10 (IL-10) played a key role in mediating the effects of BM-hMSC in our PCOS models. We demonstrated that BM-hMSC treatment was improve in metabolic and reproductive markers in our PCOS model and able to restore fertility. Conclusion: Our study demonstrates for the first time the efficacy of intra-ovarian injection of BM-hMSC or its secretome to treat PCOS-related phenotypes, including both metabolic and reproductive dysfunction. This approach may represent a novel therapeutic option for women with PCOS. Our results suggest that BM-hMSC can reverse PCOS-induced inflammation through IL-10 secretion. BM-hMSC might be a novel and robust therapeutic approach for PCOS treatment.

scholarly journals MO330ACTIVATION OF Β2 ADRENERGIC RECEPTOR SIGNALING IN MACROPHAGES BLOCKS SYSTEMIC INFLAMMATION AND PROTECTS AGAINST RENAL ISCHEMIA/REPERFUSION INJURY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sho Hasegawa ◽  
Tsuyoshi Inoue ◽  
Masaomi Nangaku ◽  
Reiko Inagi
Keyword(s):  
Rna Sequencing ◽  
Systemic Inflammation ◽  
Adrenergic Receptor ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Tissue ◽  
Β2 Adrenergic Receptor ◽  
Anti Inflammatory

Abstract Background and Aims The sympathetic nervous system regulates immune cell dynamics. However, the detailed role of sympathetic signaling in inflammatory diseases is still unclear because it varies according to the disease situation and responsible cell types. Here, we focused on sympathetic signaling in macrophages and sought to determine its detailed roles in lipopolysaccharide (LPS)-induced systemic inflammation and renal ischemia/reperfusion injury (IRI). Method In vitro, RAW 264.7 cells and murine peritoneal macrophages were used to determine the effects of β2 adrenergic receptor (Adrb2) signaling on LPS-induced proinflammatory cytokine (tumor necrosis factor-α; TNF-α) production. We also identified the critical gene that mediates the anti-inflammatory effect of Adrb2 signaling by RNA-sequencing. In vivo, we examined the effects of salbutamol (a selective Adrb2 agonist) in LPS-induced systemic inflammation and renal IRI. The involvement of macrophage Adrb2 signaling was confirmed by macrophage-specific Adrb2 conditional knockout (cKO) mice and adoptive transfer of salbutamol-treated macrophages. We also performed single-cell RNA sequencing of renal tissue to analyze the renoprotective role of salbutamol-treated macrophages in detail. Results In vitro, norepinephrine, a sympathetic neurotransmitter, suppressed LPS-induced TNF-α production in macrophages. This anti-inflammatory effect was also induced by salbutamol and reversed by butoxamine (a selective Adrb2 antagonist) in a dose-dependent manner, indicating the importance of Adrb2 in this process. RNA sequencing of these macrophages revealed that T-cell immunoglobulin and mucin-3 (Tim3) expressions were upregulated by the activation of Adrb2 signaling, which partially mediated the anti-inflammatory phenotypic alteration in macrophages. In vivo, salbutamol administration mitigated LPS-induced systemic inflammation and protected against renal IRI; this protection was mitigated in macrophage-specific Adrb2 cKO mice. Adoptive transfer of salbutamol-treated macrophages also protected against renal IRI (Figure 1). Single-cell RNA sequencing revealed that this protection was associated with the accumulation of Tim3-expressing macrophages in the renal tissue. Conclusion The activation of β2 adrenergic receptor signaling in macrophages induces anti-inflammatory phenotypic alterations partially via the induction of Tim3 expressions, which blocks LPS-induced systemic inflammation and protects against renal IRI.

Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10

Blood ◽  
2003 ◽  
Vol 101 (2) ◽  
pp. 729-738 ◽  
Author(s):  
Dominique Berrebi ◽  
Stefano Bruscoli ◽  
Nicolas Cohen ◽  
Arnaud Foussat ◽  
Graziella Migliorati ◽  
...  
Keyword(s):  
Gene Expression ◽  
Leucine Zipper ◽  
Nuclear Factor Κb ◽  
Interleukin 10 ◽  
Delayed Type Hypersensitivity ◽  
Glucocorticoid Treatment ◽  
Inflammatory Protein ◽  
Anti Inflammatory

Glucocorticoids and interleukin 10 (IL-10) prevent macrophage activation. In murine lymphocytes, glucocorticoids induce expression of glucocorticoid-induced leucine zipper (GILZ), which prevents the nuclear factor κB (NF-κB)–mediated activation of transcription. We investigated whether GILZ could account for the deactivation of macrophages by glucocorticoids and IL-10. We found that GILZ was constitutively produced by macrophages in nonlymphoid tissues of humans and mice. Glucocorticoids and IL-10 stimulated the production of GILZ by macrophages both in vitro and in vivo. Transfection of the macrophagelike cell line THP-1 with the GILZ gene inhibited the expression of CD80 and CD86 and the production of the proinflammatory chemokines regulated on activation normal T-cell expressed and secreted (CCL5) and macrophage inflammatory protein 1α (CCL3). It also prevented toll-like receptor 2 production induced by lipopolysaccharide, interferonγ, or an anti-CD40 mAb, as well as NF-κB function. In THP-1 cells treated with glucocorticoids or IL-10, GILZ was associated with the p65 subunit of NF-κB. Activated macrophages in the granulomas of patients with Crohn disease or tuberculosis do not produce GILZ. In contrast, GILZ production persists in tumor-infiltrating macrophages in Burkitt lymphomas. Therefore, GILZ appears to play a key role in the anti-inflammatory and immunosuppressive effects of glucocorticoids and IL-10. Glucocorticoid treatment stimulates GILZ production, reproducing an effect of IL-10, a natural anti-inflammatory agent. The development of delayed-type hypersensitivity reactions is associated with the down-regulation of GILZ gene expression within lesions. In contrast, the persistence of GILZ gene expression in macrophages infiltrating Burkitt lymphomas may contribute to the failure of the immune system to reject the tumor.

scholarly journals Role of Peroxisome Proliferator-Activated Receptors in Inflammation Control

2004 ◽  
Vol 2004 (3) ◽  
pp. 156-166 ◽  
Author(s):  
Jihan Youssef ◽  
Mostafa Badr
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Late Phase ◽  
Common Mechanism ◽  
Peroxisome Proliferator ◽  
Initiation Phase ◽  
Anti Inflammatory ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) were discovered over a decade ago, and were classified as orphan members of the nuclear receptor superfamily. To date, three PPAR subtypes have been discovered and characterized (PPARα, β/δ, γ). Different PPAR subtypes have been shown to play crucial roles in important diseases and conditions such as obesity, diabetes, atherosclerosis, cancer, and fertility. Among the most studied roles of PPARs is their involvement in inflammatory processes. Numerous studies have revealed that agonists of PPARα and PPARγ exert anti-inflammatory effects both in vitro and in vivo. Using the carrageenan-induced paw edema model of inflammation, a recent study in our laboratories showed that these agonists hinder the initiation phase, but not the late phase of the inflammatory process. Furthermore, in the same experimental model, we recently also observed that activation of PPARδ exerted an anti-inflammatory effect. Despite the fact that exclusive dependence of these effects on PPARs has been questioned, the bulk of evidence suggests that all three PPAR subtypes, PPARα,δ,γ, play a significant role in controlling inflammatory responses. Whether these subtypes act via a common mechanism or are independent of each other remains to be elucidated. However, due to the intensity of research efforts in this area, it is anticipated that these efforts will result in the development of PPAR ligands as therapeutic agents for the treatment of inflammatory diseases.

In Vivo and In Vitro Toxicodynamic Analyses of New Quinolone-and Nonsteroidal Anti-Inflammatory Drug-Induced Effects on the Central Nervous System

1999 ◽  
Vol 43 (8) ◽  
pp. 2101-2101
Author(s):  
Hideki Kita ◽  
Hirotami Matsuo ◽  
Hitomi Takanaga ◽  
Junichi Kawakami ◽  
Koujirou Yamamoto ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Drug Induced ◽  
Inflammatory Drug ◽  
The Central Nervous System ◽  
Anti Inflammatory

scholarly journals Mesenchymal stem cell therapy ameliorates metabolic dysfunction and restores fertility in a PCOS mouse model through interleukin-10

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rishi Man Chugh ◽  
Hang-soo Park ◽  
Abdeljabar El Andaloussi ◽  
Amro Elsharoud ◽  
Sahar Esfandyari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Polycystic Ovary ◽  
Therapeutic Option ◽  
Interleukin 10 ◽  
Reproductive Age ◽  
Mesenchymal Stem Cell Therapy ◽  
Anti Inflammatory

Abstract Background Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-age women. Excessive inflammation and elevated androgen production from ovarian theca cells are key features of PCOS. Human bone marrow mesenchymal stem cells (BM-hMSC) and their secreted factors (secretome) exhibit robust anti-inflammatory capabilities in various biological systems. We evaluated the therapeutic efficacy of BM-hMSC and its secretome in both in vitro and in vivo PCOS models. Methods For in vitro experiment, we treated conditioned media from BM-hMSC to androgen-producing H293R cells and analyzed androgen-producing gene expression. For in vivo experiment, BM-hMSC were implanted into letrozole (LTZ)-induced PCOS mouse model. BM-hMSC effect in androgen-producing cells or PCOS model mice was assessed by monitoring cell proliferation (immunohistochemistry), steroidogenic gene expression (quantitative real-time polymerase chain reaction [qRT-PCR] and Western blot, animal tissue assay (H&E staining), and fertility by pup delivery. Results BM-hMSC significantly downregulate steroidogenic gene expression, curb inflammation, and restore fertility in treated PCOS animals. The anti-inflammatory cytokine interleukin-10 (IL-10) played a key role in mediating the effects of BM-hMSC in our PCOS models. We demonstrated that BM-hMSC treatment was improved in metabolic and reproductive markers in our PCOS model and able to restore fertility. Conclusion Our study demonstrates for the first time the efficacy of intra-ovarian injection of BM-hMSC or its secretome to treat PCOS-related phenotypes, including both metabolic and reproductive dysfunction. This approach may represent a novel therapeutic option for women with PCOS. Our results suggest that BM-hMSC can reverse PCOS-induced inflammation through IL-10 secretion. BM-hMSC might be a novel and robust therapeutic approach for PCOS treatment.

scholarly journals Development of Tannin-bridged Cerium Oxide Microcubes-chitosan Cryogel as a Multifunctional Wound Dressing

2021 ◽  
Author(s):  
Muzhou Teng ◽  
Zhijia Li ◽  
Zhihui Lu ◽  
Keke Wu ◽  
Jinshan Guo
Keyword(s):  
Wound Healing ◽  
Wound Dressing ◽  
Bacterial Infections ◽  
Inflammatory Cytokine ◽  
Interleukin 10 ◽  
Sprague Dawley ◽  
Necrosis Factor Alpha ◽  
Anti Inflammatory

Abstract Background: Efficient resolution of oxidative stress, inflammation and bacterial infections are crucial for wound healing. To surmount these problems, tannic acid (TA)-bridged CeO2 microcubes and chitosan (CS) (CS-TA@CeO2) cryogel was fabricated through hydrogen bonding interactions as a multifunctional wound dressing. Results: The physicochemical characterizations confirmed the successful introduction and uniform incorporation of TA@CeO2 microcubes into CS network. Thus-obtained CS-TA@CeO2 cryogels displayed suitable porous structure and swelling ratio. The CS-TA@CeO2 cryogels exhibited favorable antioxidant ability evidenced by scavenging more than 82.9% ROS in vitro and significantly increasing the antioxidant enzyme levels in vivo. The anti-inflammatory ability of the cryogels was confirmed by the downregulated expression of the inflammatory cytokine, tumor necrosis factor-alpha (TNF-α) and the upregulated expression of the anti-inflammatory cytokine, interleukin-10 (IL-10). The multifunctional cryogels also showed excellent antibacterial activities against Gram-positive (S.aureus) and Gram-negative (E.coli) bacteria. Furthermore, the cryogels can promote the adhesion and proliferation of mouse fibroblasts (L929) cells. Moreover, CS-TA@CeO2 cryogels presented excellent hemostatic performance in rat tail amputation model. In vivo Sprague-Dawley (SD) rats full-thickness experiments illustrated that the cryogels can significantly accelerate wound healing through providing considerable antioxidant activity, promoting angiogenesis, and increasing collagen deposition. Conclusions: Overall, the multifunctional CS-TA@CeO2 cryogels showed great potential for wound healing.

scholarly journals Evaluation of Anti-Inflammatory Activities of a Triterpene β-Elemonic Acid in Frankincense In Vivo and In Vitro

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1187 ◽  
Author(s):  
Yue Zhang ◽  
Ying-li Yu ◽  
Hua Tian ◽  
Ru-yu Bai ◽  
Ya-nan Bi ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Interleukin 10 ◽  
The Body ◽  
Raw264.7 Cells ◽  
Control Group ◽  
Intragastric Administration ◽  
Dependent Manner ◽  
Anti Inflammatory

The purpose of this research was to extract and separate the compounds from frankincense, and then evaluate their anti-inflammatory effects. The isolated compound was a representative tetracyclic triterpenes of glycine structure according to 1H-NMR and 13C-NMR spectra, which is β-elemonic acid (β-EA). We determined the content of six different localities of frankincense; the average content of β-EA was 41.96 mg/g. The toxic effects of β-EA administration (400, 200, 100 mg/kg) for four weeks in Kunming (KM) mice were observed. Compared with the control group, the body weight of mice, the visceral coefficients and serum indicators in the β-EA groups showed no systematic variations. The anti-inflammatory effects of β-EA were evaluated in LPS-induced RAW264.7 cells, xylene-induced induced ear inflammation in mice, carrageenin-induced paw edema in mice, and cotton pellet induced granuloma formation in rats. β-EA inhibited overproduction of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1), soluble TNF receptor 1 (sTNF R1), Eotaxin-2, Interleukin 10 (IL-10) and granulocyte colony-stimulating factor (GCSF) in the RAW264.7 cells. Intragastric administration with β-EA (300, 200, and 100 mg/kg in mice, and 210, 140, and 70 mg/kg in rats) all produced distinct anti-inflammatory effects in vivo in a dose-dependent manner. Following treatment with β-EA (300 mg/kg, i.g.), the NO level in mice ears and PGE2 in mice paws both decreased (p < 0.01). In conclusion, our study indicates that β-EA could be a potential anti-inflammatory agent for the treatment of inflammatory diseases.

Sign in / Sign up

Export Citation Format

Share Document