NCS 613 exhibits anti-inflammatory effects on PBMCs from lupus patients by inhibiting p38 MAPK and NF-κB signalling pathways while reducing proinflammatory cytokine production

2013 ◽  
Vol 91 (5) ◽  
pp. 353-361 ◽  
Author(s):  
Issaka Yougbaré ◽  
Gilles Boire ◽  
Michelle Roy ◽  
Claire Lugnier ◽  
Éric Rouseau
Keyword(s):  
P38 Mapk ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Pde4 Inhibitor ◽  
Human Pbmcs ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Tnf Α ◽  
Anti Inflammatory

Systemic lupus erythematosus (SLE) is a polymorphic and multigenic autoimmune disease that evolves into progressive and chronic inflammation of multiple joints and organs. Phosphorylation and activation of p38 MAPK, along with the resulting overproduction of interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α is a hallmark of inflammatory disorders. Here, we investigated the anti-inflammatory pathway modulated by NCS 613, a specific PDE4 inhibitor, on human peripheral blood mononuclear cells (PBMCs) from 5 healthy donors and 12 SLE patients. PDE4 subtypes, p38 MAPK, and IκBα protein levels were analyzed by Western blot, while NF-κB and PDE4B immunostaining was assessed in control and lipopolysaccharide (LPS) -pretreated PBMCs. Proinflammatory cytokines were quantified by ELISA, while IL-1β mRNA was resolved by RT–qPCR. NCS 613 treatment decreased PDE4B and upregulated PDE4C in human PBMCs from healthy donors and SLE patients. LPS stimulation increased p38 MAPK phosphorylation and NF-κB translocation to the nucleus, which was abolished by NCS 613 treatment. Concomitantly, NCS 613 restored IκBα detection levels in human PBMCs from both healthy donors and SLE patients. This compound also abolished LPS-induced inflammation in PBMCs by reducing IL-6, IL-8, and TNF-α cytokines. NCS 613 is a small molecule displaying anti-inflammatory properties that may provide an alternative or complementary strategy for SLE management.

Dipyridamole decreases inflammatory metalloproteinase-9 expression and release by human monocytes

2013 ◽  
Vol 109 (02) ◽  
pp. 280-289 ◽  
Author(s):  
Maria Annunziata Carluccio ◽  
Mariangela Pellegrino ◽  
Nadia Calabriso ◽  
Carlo Storelli ◽  
Giuseppe Martines ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Mononuclear Cells ◽  
Nuclear Translocation ◽  
Human Peripheral Blood ◽  
Antiplatelet Agent ◽  
Guanosine Monophosphate ◽  
Human Monocytes ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Anti Inflammatory

SummaryMatrix metalloproteinase (MMP)-9 plays an important role in stroke by accelerating matrix degradation, disrupting the blood-brain barrier and increasing infarct size. Dipyridamole is an antiplatelet agent with recognised benefits in ischaemic stroke prevention. In addition to its antiplatelet properties, recent studies have reported that dipyridamole also features anti-inflammatory and anti-oxidant properties. We therefore investigated whether dipyridamole can ameliorate the proinflammatory profile of human monocytes, a source of MMP-9 in stroke, in terms of regulation of MMP-9 activity and expression, and explored underlying mechanisms. Human peripheral blood mononuclear cells (PBMC) and U937 cells were treated with increasing concentrations of dipyridamole (up to 10 µg/ml) for 60 minutes before stimulation with tumour necrosis factor (TNF)-α or phorbol myristate acetate (PMA). Exposure of PBMC and U937 to dipyridamole reduced TNF-α- and PMA-induced MMP-9 activity and protein release as well as MMP-9 mRNA, without significantly affecting the release of TIMP-1. This inhibitory effect was independent of dipyridamole-induced cyclic adeno-sine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) increase. Correspondingly, dipyridamole also significantly inhibited TNF-α-induced nuclear factor (NF)-κB activation and nuclear translocation of the p65 NF-κB subunit through a mechanism involving the inhibition of IkBα degradation and p38 MAPK activation. In conclusion, dipyridamole, at therapeutically achievable concentrations, reduces the expression and release of MMP-9 through a mechanism involving p38 MAPK and NF-κB inhibition. These results indicate that dipyridamole exerts anti-inflammatory properties in human monocytes that may favourably contribute to its actions in the secondary prevention of stroke, independent of its antiplatelet properties.

scholarly journals Differential In Vitro Cytokine Induction by the Species of Cryptococcus gattii Complex

2018 ◽  
Vol 86 (4) ◽  
Author(s):  
Patricia F. Herkert ◽  
Jessica C. dos Santos ◽  
Ferry Hagen ◽  
Fatima Ribeiro-Dias ◽  
Flávio Queiroz-Telles ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Sensu Stricto ◽  
Cryptococcus Gattii ◽  
The Other ◽  
Human Pbmcs ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α

ABSTRACT Cryptococcal species vary in capsule and cell size, thermotolerance, geographic distribution, and affected populations. Cryptococcus gattii sensu stricto and C. deuterogattii affect mainly immunocompetent hosts; however, C. bacillisporus , C. decagattii , and C. tetragattii cause infections mainly in immunocompromised hosts. This study aimed to compare the capacities of different species of the C. gattii species complex to induce cytokines and antimicrobial molecules in human peripheral blood mononuclear cells (PBMCs). Cryptococcus bacillisporus and C. deuterogattii induced the lowest levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 among the five species of the C. gattii complex. Cryptococcus deuterogattii induced higher levels of IL-22 than those induced by C. tetragattii and the environmental species C. flavescens . In addition, C. bacillisporus and C. gattii sensu stricto proliferated inside human monocyte-derived macrophages after 24 h of infection. All Cryptococcus species were able to generate reactive oxygen species (ROS) in human PBMCs, with C. bacillisporus and C. deuterogattii being more efficient than the other species. In conclusion, C. bacillisporus and C. deuterogattii induce lower levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 and higher ROS levels than those induced by the other species. Species of the Cryptococcus gattii complex have different abilities to induce cytokine and ROS production by human PBMCs.

scholarly journals Rare Acetogenins with Anti-Inflammatory Effect from the Red Alga Laurencia obtusa

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 476
Author(s):  
Walied Alarif ◽  
Sultan Al-Lihaibi ◽  
Nahed Bawakid ◽  
Ahmed Abdel-Lateff ◽  
Hamdan Al-malky
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Red Alga ◽  
Peripheral Blood Mononuclear ◽  
Organic Extract ◽  
Chemical Structures ◽  
Data Analyses ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Three new rare C12 acetogenins (enyne derivatives 1–3) were isolated from the organic extract obtained from the red alga Laurencia obtusa, collected from the Red Sea. The chemical structures of the isolated compounds were established by spectroscopical data analyses. Potent anti-inflammatory effect of the isolated metabolites was evidenced by inhibition of the release of inflammatory mediators (e.g., TNF-α, IL-1β and IL-6) by employing Human Peripheral Blood Mononuclear Cells (PBMC).

scholarly journals Receptor Recognition of and Immune Intracellular Pathways for Veillonella parvula Lipopolysaccharide

2009 ◽  
Vol 16 (12) ◽  
pp. 1804-1809 ◽  
Author(s):  
Giovanni Matera ◽  
Valentina Muto ◽  
Maria Vinci ◽  
Emilia Zicca ◽  
Shahla Abdollahi-Roodsaz ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Cytokine Induction ◽  
Tnf Α ◽  
Intracellular Pathways

ABSTRACT Veillonella parvula is an anaerobic gram-negative coccus that is part of the normal flora of the animal and human mouth and gastrointestinal and genitourinary tracts. Oral V. parvula is involved in the development of early periodontal disease as well as different types of serious infections. Present data on molecular mechanisms responsible for innate immune response against Veillonella are very scanty. The aim of this study was to investigate the Toll-like receptor (TLR) pathways responsible for V. parvula lipopolysaccharide (LPS) and to identify the intracellular pathways induced by this recognition. V. parvula LPS stimulated tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) release in human peripheral blood mononuclear cells (PBMC) in a dose-dependent manner. Pretreatment of cells with a TLR4 antagonist significantly reduced TNF-α and IL-6 production in PBMC stimulated with either Veillonella or Escherichia coli LPS. However, V. parvula LPS was 10- to 100-fold less active than E. coli LPS for cytokine induction. TNF-α, IL-1β, IL-6, and IL-10 were released in wild-type and TLR2−/−, but not TLR4−/−, mouse macrophage cultures. V. parvula LPS was able to activate the human PBMC p38 mitogen-activated protein kinase (MAPK). A specific p38 MAPK inhibitor strongly inhibited V. parvula LPS-induced TNF-α, IL-1β, IL-6, and IL-10. In conclusion, V. parvula LPS is able to induce cytokine production in both human and murine in vitro models, although it is less effective than Enterobacteriaceae LPS. V. parvula LPS-stimulated cytokine induction, as well as p38 MAPK activation, are TLR4-dependent features.

Candida tropicalis induces pro-inflammatory cytokine production, NF-κB and MAPKs pathways regulation, and dectin-1 activation

2018 ◽  
Vol 64 (12) ◽  
pp. 937-944 ◽  
Author(s):  
Zhimin Duan ◽  
Qing Chen ◽  
Rong Zeng ◽  
Leilei Du ◽  
Caixia Liu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Inflammatory Cytokine ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Downstream Signaling ◽  
Tnf Α ◽  
Mitogen Activated Protein

The prevalence of Candida infection induced by non-albicans Candida (NAC) species is increasing. However, as a common NAC species, C. tropicalis has received much less study in terms of host immunity than C. albicans has. In this study, we evaluated the pro-inflammatory cytokine responses evoked by C. tropicalis and determined whether dectin-1 and downstream NF-κB and mitogen-activated protein kinases (MAPKs) signaling pathways played roles in inflammation in human peripheral blood mononuclear cells (PBMCs) and THP-1 macrophage-like cells. Exposure of PBMCs and THP-1 macrophage-like cells to C. tropicalis led to the enhanced gene expression and secretion of TNF-α and IL-6 in a time- and dose-dependent manner. THP-1 macrophage-like cells being challenged by C. tropicalis resulted in the activation of the NF-κB, p38, and ERK1/2 MAPK signaling pathways. We also found that the expression of dectin-1 was increased with C. tropicalis treatment. These data reveal that dectin-1 may play a role in sensing the inflammation response induced by C. tropicalis and that NF-κB and MAPK are involved in the downstream signaling pathways in macrophages.

scholarly journals Liposome/gold hybrid nanoparticle encoded with CoQ10 (LGNP-CoQ10) suppressed rheumatoid arthritis via STAT3/Th17 targeting

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241080
Author(s):  
Jooyeon Jhun ◽  
Jeonghyeon Moon ◽  
Jaeyoon Ryu ◽  
Yonghee Shin ◽  
Seangyoun Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Therapeutic Potential ◽  
Human Peripheral Blood ◽  
Treated Group ◽  
Hybrid Nanoparticles ◽  
Peripheral Blood Mononuclear ◽  
Hematoxylin And Eosin ◽  
Anti Inflammatory ◽  
Safranin O

Coenzyme Q10 (CoQ10), also known as ubiquinone, is a fat-soluble antioxidant. Although CoQ10 has not been approved as medication by the Food and Drug Administration, it is widely used in dietary supplements. Some studies have shown that CoQ10 has anti-inflammatory effects on various autoimmune disorders. In this study, we investigated the anti-inflammatory effects of liposome/gold hybrid nanoparticles encoded with CoQ10 (LGNP-CoQ10). Both CoQ10 and LGNP-CoQ10 were administered orally to mice with collagen-induced arthritis (CIA) for 10 weeks. The inflammation pathology of joint tissues of CIA mice was then analyzed using hematoxylin and eosin and Safranin O staining, as well as immunohistochemistry analysis. We obtained immunofluorescence staining images of spleen tissues using confocal microscopy. We found that pro-inflammatory cytokines were significantly decreased in LGNP-CoQ10 injected mice. Th17 cell and phosphorylated STAT3-expressed cell populations were also decreased in LGNP-CoQ10 injected mice. When human peripheral blood mononuclear cells (PBMCs) were treated with CoQ10 and LGNP-CoQ10, the IL-17 expression of PBMCs in the LGNP-CoQ10-treated group was significantly reduced. Together, these results suggest that LGNP-CoQ10 has therapeutic potential for the treatment of rheumatoid arthritis.

scholarly journals IL-38: A New Player in Inflammatory Autoimmune Disorders

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 345 ◽  
Author(s):  
Lihui Xie ◽  
Zhaohao Huang ◽  
He Li ◽  
Xiuxing Liu ◽  
Songguo Zheng ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Autoimmune Disorders ◽  
Current Data ◽  
Peripheral Blood Mononuclear ◽  
Anti Inflammatory ◽  
Inflammatory Autoimmune Diseases

Interleukin (IL)-38, a newly discovered IL-1 family cytokine, is expressed in several tissues and secreted by various cells. IL-38 has recently been reported to exert an anti-inflammatory function by binding to several receptors, including interleukin-36 receptor (IL-36R), interleukin-1 receptor accessory protein-like 1 (IL-1RAPL1), and interleukin-1 receptor 1 (IL-1R1) to block binding with other pro-inflammatory cytokines and inhibit subsequent signaling pathways; thereby regulating the differentiation and function of T cells, peripheral blood mononuclear cells, macrophages, and dendritic cells. Inflammatory autoimmune diseases, which are common immune-mediated inflammatory syndromes, are characterized by an imbalance between T helper cells (Ths), especially Th1s and Th17s, and regulatory T cells (Tregs). Recent findings have shown that abnormal expression of IL-38 in inflammatory autoimmune diseases, such as rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, primary Sjogren’s syndrome, psoriasis, inflammatory bowel disease, hidradenitis suppurativa, ankylosing spondylitis, and glaucoma, involves Th1s, Th17s, and Tregs. In this review, the expression, regulation, and biological function of IL-38 are discussed, as are the roles of IL-38 in various inflammatory autoimmune disorders. Current data support that the IL-38/IL-36R and/or IL-38/IL-1RAPL1 axis primarily play an anti-inflammatory role in the development and resolution of inflammatory autoimmune diseases and indicate a possible therapeutic benefit of IL-38 in these diseases.

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