scholarly journals Mast Cell Cytokines IL-1, IL-33, and IL-36 Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-Inflammatory Cytokines IL-37, IL-38, and IL-1Ra

2021 ◽  
Vol 22 (15) ◽  
pp. 8076
Author(s):  
Pio Conti ◽  
Fabrizio E. Pregliasco ◽  
Rosa G. Bellomo ◽  
Carla E. Gallenga ◽  
Alessandro Caraffa ◽  
...  
Keyword(s):  
Immune Cells ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Joint Inflammation ◽  
Skin Inflammation ◽  
Dramatic Improvement ◽  
Keratinocyte Proliferation ◽  
Human Mononuclear Cells ◽  
Th17 Lymphocytes

Psoriasis (PS) is a skin disease with autoimmune features mediated by immune cells, which typically presents inflammatory erythematous plaques, and is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells, including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature, and reside in vascularized tissues. They can be activated by antigen-provoking overexpression of proinflammatory cytokines, and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophages to release IL-36—a powerful proinflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic proinflammatory diseases such as psoriasis. Suppression of IL-36 could result in a dramatic improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra, which binds to IL-36 receptor ligands, but suppression can also occur by binding IL-38 to the IL-36 receptor (IL-36R). IL-38 specifically binds only to IL-36R, and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs—a process that activates macrophages to secrete proinflammatory IL-36 inhibited by IL-38. IL-37 belongs to the IL-1 family, and broadly suppresses innate inflammation via IL-1 inhibition. IL-37, in murine models of inflammatory arthritis, causes the suppression of joint inflammation through the inhibition of IL-1. Therefore, it is pertinent to think that IL-37 can play an inhibitory role in inflammatory psoriasis. In this article, we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis, and hold promise as an innovative therapeutic tool.

scholarly journals Mast Cells Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-inflammatory Cytokines IL-37, IL-38 and IL-1Ra

2021 ◽  
Author(s):  
Pio Conti ◽  
Fabrizio Pregliasco ◽  
Rosa G. Bellomo ◽  
Carla E. Gallenga ◽  
Alessandro Caraffa ◽  
...  
Keyword(s):  
Mast Cells ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Inflammatory Diseases ◽  
Skin Inflammation ◽  
Keratinocyte Proliferation ◽  
Th17 Lymphocytes

Psoriasis (PS) is an autoimmune skin disease mediated by immune cells that typically presents inflammatory erythematous plaques, and it is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature and reside in vascularized tissues. They can be activated by antigen provoking overexpression of pro-inflammatory cytokines and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophage to release IL-36, a powerful pro-inflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic pro-inflammatory diseases such as psoriasis. Suppressing IL-36 results in a noticeable improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra which binds on to IL-36 receptor ligand, but suppression can also occur by binding IL-38 to the IL-36R receptor. IL-38 specifically binds only to IL-36R and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs, a process that activates macrophages to secrete pro-inflammatory IL-36 inhibited by IL-38. In this article we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis and hold promise of an innovative therapeutic tool.

The effect of 1,25(OH)2D3 on interferon i secretion by human mononuclear cells in vitro

2017 ◽  
Author(s):  
Lambros Athanassiou ◽  
Andrianos Nezos ◽  
Ifigenia Kostoglou-Athanassiou ◽  
Clio Mavragani ◽  
Panagiotis Athanassiou ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Mononuclear Cells

scholarly journals Investigation of Mitochondrial Transfer between Human Erythroblasts

2021 ◽  
Author(s):  
◽  
Brittany Lewer
Keyword(s):  
Bone Marrow ◽  
Mitochondrial Dna ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Qpcr Assay ◽  
Dna Polymorphisms ◽  
Mitochondrial Transfer ◽  
Hel Cells ◽  
Allele Specific

<p>The increasingly studied phenomenon of mitochondria transferring between cells contrasts the popular belief that mitochondria reside permanently within their cells of origin. Research has identified this process occurring in many tissues such as brain, lung and more recently within the bone marrow. This project aimed to investigate if mitochondria could be transferred between human erythroblasts, a context not previously studied.  Tissue microenvironments can be modelled using co-culture systems. Fluorescence activated cell sorting and a highly sensitive Allele-Specific-Blocker qPCR assay were used to leverage mitochondrial DNA polymorphisms between co-cultured populations. Firstly, HL-60ρ₀ bone marrow cells, without mitochondrial DNA, deprived of essential nutrients pyruvate and uridine were co-cultured in vitro with HEL cells, a human erythroleukemia. Secondly, HEL cells treated with deferoxamine or cisplatin, were cocultured with parental HL-60 cells in vitro. Lastly, ex vivo co-cultures between erythroblasts differentiated from mononuclear cells in peripheral blood were conducted, where one population was treated with deferoxamine.  Co-culture was able to improve recovery when HL-60ρ₀ cells were deprived of pyruvate and uridine. Improved recovery was similarly detected for HEL cells treated with deferoxamine after co-culture with HL-60 cells. Transfer of mitochondrial DNA did not occur at a detectable level in any co-culture condition tested. The high sensitivity of the allele-specific-blocker qPCR assay required completely pure populations to analyse, however this was not achieved using FACS techniques. In conclusion, results have not demonstrated but cannot exclude the possibility that erythroid cells transfer mitochondria to each other.</p>

Effects of 200cH medications on mice bone marrow cells and macrophages

2021 ◽  
Vol 10 (35) ◽  
pp. 75-76
Author(s):  
Carolina De Oliveira ◽  
Ana Paula R. Abud ◽  
Eneida Da Lozzo ◽  
Raffaello Di Bernardi ◽  
Simone De Oliveira ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Cells ◽  
Bone Marrow Cells ◽  
Ex Vivo ◽  
Hematopoietic Lineage ◽  
Lineage Markers ◽  
Lachesis Muta ◽  
Nonadherent Cells ◽  
Marrow Cells

Paracelsus once wrote: "All things are poison and nothing is without poison, only the dose permits something not to be poisonous." Latter Hahnemann formulated the law of similars, preparations which cause certain symptoms in healthy individuals if given in diluted form to patients exhibiting similar symptoms will cure it. Highly diluted natural complexes prepared according to Hahnemann’s ancient techniques may represent a new form of immunomodulatory therapy. The lack of scientific research with highly diluted products led us to investigate the in vivo and in vitro actions of commonly used medications. Here we describe the results of experimental studies aimed at verifying the effects of Mercurius solubilis, Atropa Belladonna, Lachesis muta and Bryonia alba. All medications were at 200cH dilution. Animals were maintained for 7 days and were allowed to drink the medications, which were prepared in a way that the final dilution and agitation (200cH) was performed in drinking water. The medication bottle was changed and sucussed every afternoon. Co-culture of non treated mice bone marrow cells and in vitro treated peritoneal macrophages were also performed. After animal treatment the bone marrow cells were immunophenotyped with hematopoietic lineage markers on a flow cytometer. We have determined CD11b levels on bone marrow cells after culture and co-culture with treated macrophages and these macrophages were processed to scanning electron microscopy. We have observed by morphological changes that macrophages were activated after all treatments. Mercurius solubilis treated mice showed an increase in CD3 expression and in CD11b on nonadherent bone marrow cells after co-culture with in vitro treatment. Atropa Belladonna increased CD45R and decreased Ly-6G expression on bone marrow cells after animal treatment. Lachesis muta increased CD3, CD45R and, CD11c expression and decreased CD11b ex vivo and in nonadherent cells from co-culture. Bryonia alba increased Ly-6G, CD11c and CD11b expression ex vivo and when in co-culture CD11b was increased in adherent cells as well as decreased in nonadherent cells. With these results we have demonstrated that highly diluted medications act on immune cells activating macrophages, and changing the expression profile of hematopoietic lineage markers. Highly diluted medications are less toxic and cheaper than other commonly used medications and based on our observations, it is therefore conceivable that this medications which are able to act on bone marrow and immune cells may have a potential therapeutic use in clinical applications in diseases were the immune system is affected and also as regenerative medicine as it may allow proliferation and differentiation of progenitor cells.

scholarly journals Glucocorticoids and Catecholamines Affect in Vitro Functionality of Porcine Blood Immune Cells

Animals ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 545 ◽  
Author(s):  
Lena Reiske ◽  
Sonja Schmucker ◽  
Julia Steuber ◽  
Volker Stefanski
Keyword(s):  
Immune Cells ◽  
Lymphocyte Proliferation ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Intracellular Cytokine Staining ◽  
Stress Hormones ◽  
High Stress ◽  
Peripheral Blood Mononuclear ◽  
Indwelling Catheters

Stress hormones exert important modulating influences on the functionality of immune cells. Despite its major role as a livestock animal and its increasing use as an animal model, knowledge about this relationship in the domestic pig is rare. This study therefore aimed to characterize the effect of glucocorticoids and catecholamines on the proliferation and cytokine production of porcine peripheral blood mononuclear cells (PBMC). Blood was obtained from donor pigs equipped with indwelling catheters to exclude stress hormone exposition before in vitro testing. PBMC were stimulated in the presence of cortisol, adrenaline or noradrenaline at concentrations resembling low to high stress conditions. Proliferation was determined via 3H-thymidine incorporation, and TNFα producers were quantified by intracellular cytokine staining. Cortisol led to a decrease in mitogen-induced lymphocyte proliferation and the number of TNFα producing cells. In contrast, catecholamines increased proliferation while exerting repressive or no effects on the number of cytokine producers. Remarkably, in concentrations presumably found in lymphatic tissue in stress situations, noradrenaline suppressed lymphocyte proliferation completely. The shown repressive effects might especially have implications on health and welfare in pigs. The obtained results provide a preliminary database for extended studies on the molecular mechanisms of glucocorticoid and catecholamine actions on porcine immune cells.

scholarly journals A Limulus Antilipopolysaccharide Factor-Derived Peptide Exhibits a New Immunological Activity with Potential Applicability in Infectious Diseases

2000 ◽  
Vol 7 (4) ◽  
pp. 669-675 ◽  
Author(s):  
Maribel G. Vallespi ◽  
Luis A. Glaria ◽  
Osvaldo Reyes ◽  
Hilda E. Garay ◽  
Joel Ferrero ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Cyclic Peptides ◽  
Mononuclear Cells ◽  
Therapeutic Potential ◽  
Peritoneal Macrophages ◽  
Induced Response ◽  
No Production ◽  
Human Mononuclear Cells

ABSTRACT Previous studies have shown that cyclic peptides corresponding to residues 35 to 52 of the Limulus antilipopolysaccharide (anti-LPS) factor (LALF) bind and neutralize LPS-mediated in vitro and in vivo activities. Therapeutic approaches based on agents which bind and neutralize LPS activities are particularly attractive because these substances directly block the primary stimulus for the entire proinflammatory cytokine cascade. Here we describe new activities of the LALF31–52 peptide, other than its LPS binding ability. Surprisingly, supernatants from human mononuclear cells stimulated with the LALF peptide are able to induce in vitro antiviral effects on the Hep-2 cell line mediated by gamma interferon (IFN-γ) and IFN-α. Analysis of the effect of LALF31–52 on tumor necrosis factor (TNF) and nitric oxide (NO) production by LPS-stimulated peritoneal macrophages revealed that a pretreatment with the peptide decreased LPS-induced TNF production but did not affect NO generation. This indicates that the LALF peptide modifies the LPS-induced response. In a model in mice with peritoneal fulminating sepsis, LALF31–52 protected the mice when administered prophylactically, and this effect is related to reduced systemic TNF-α levels. This study demonstrates, for the first time, the anti-inflammatory properties of the LALF-derived peptide. These properties widen the spectrum of the therapeutic potential for this LALF-derived peptide and the molecules derived from it. These agents may be useful in the prophylaxis and therapy of viral and bacterial infectious diseases, as well as for septic shock.

Proinflammatory and osteoclastogenic effects of beta-tricalciumphosphate and hydroxyapatite particles on human mononuclear cells in vitro

Biomaterials ◽  
2009 ◽  
Vol 30 (29) ◽  
pp. 5312-5318 ◽  
Author(s):  
Tobias Lange ◽  
Arndt F. Schilling ◽  
Fabian Peters ◽  
Friedrich Haag ◽  
Michael M. Morlock ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Mononuclear Cells
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