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Article ; Online: Impaired LAIR-1-mediated immune control due to collagen degradation in fibrosis.

2024 Volume 146, Page(s) 103219

Abstract: Tissue repair is disturbed in fibrotic diseases like systemic sclerosis (SSc), where the deposition of large amounts of extracellular matrix components such as collagen interferes with organ function. LAIR-1 is an inhibitory collagen receptor highly ... ...

Abstract	Tissue repair is disturbed in fibrotic diseases like systemic sclerosis (SSc), where the deposition of large amounts of extracellular matrix components such as collagen interferes with organ function. LAIR-1 is an inhibitory collagen receptor highly expressed on tissue immune cells. We questioned whether in SSc, impaired LAIR-1-collagen interaction is contributing to the ongoing inflammation and fibrosis. We found that SSc patients do not have an intrinsic defect in LAIR-1 expression or function. Instead, fibroblasts from healthy controls and SSc patients stimulated by soluble factors that drive inflammation and fibrosis in SSc deposit disorganized collagen products in vitro, which are dysfunctional LAIR-1 ligands. This is dependent of matrix metalloproteinases and platelet-derived growth factor receptor signaling. In support of a non-redundant role of LAIR-1 in the control of fibrosis, we found that LAIR-1-deficient mice have increased skin fibrosis in response to repeated injury and in the bleomycin mouse model for SSc. Thus, LAIR-1 represents an essential control mechanism for tissue repair. In fibrotic disease, excessive collagen degradation may lead to a disturbed feedback loop. The presence of functional LAIR-1 in patients provides a therapeutic opportunity to reactivate this intrinsic negative feedback mechanism in fibrotic diseases.
Language	English
Publishing date	2024-05-01
Publishing country	England
Document type	Journal Article
ZDB-ID	639452-8
ISSN	1095-9157 ; 0896-8411
ISSN (online)	1095-9157
ISSN	0896-8411
DOI	10.1016/j.jaut.2024.103219
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Zs.A 2368: Show issues

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Article ; Online: Phoenix from the flames: Rediscovering the role of the CD40-CD40L pathway in systemic lupus erythematosus and lupus nephritis.

Ramanujam, Meera / Steffgen, Jürgen / Visvanathan, Sudha / Mohan, Chandra / Fine, Jay S / Putterman, Chaim

Autoimmunity reviews

2020 Volume 19, Issue 11, Page(s) 102668

Abstract: Lupus nephritis (LN) is a significant complication of systemic lupus erythematosus (SLE), increasing its morbidity and mortality. Although the current standard of care helps suppress disease activity, it is associated with toxicity and ultimately does ... ...

Abstract	Lupus nephritis (LN) is a significant complication of systemic lupus erythematosus (SLE), increasing its morbidity and mortality. Although the current standard of care helps suppress disease activity, it is associated with toxicity and ultimately does not cure SLE. At present, there are no therapies specifically indicated for the treatment of LN and there is an unmet need in this disease where treatment remains a challenge. The CD40-CD40L pathway is central to SLE pathogenesis and the generation of autoantibodies and their deposition in the kidneys, resulting in renal injury in patients with LN. CD40 is expressed on immune cells (including B cells, monocytes and dendritic cells) and also non-haematopoietic cells. Interactions between CD40L on T cells and CD40 on B cells in the renal interstitium are critical for the local expansion of naive B cells and autoantibody-producing B cells in LN. CD40L-mediated activation of myeloid cells and resident kidney cells, including endothelial cells, proximal tubular epithelial cells, podocytes and mesangial cells, further amplifies the inflammatory milieu in the interstitium and the glomeruli. Several studies have highlighted the upregulated expression of CD40 in LN kidney biopsies, and preclinical data have demonstrated the importance of the CD40-CD40L pathway in murine SLE and LN. Blocking this pathway is expected to ameliorate inflammation driven by infiltrating immune cells and resident kidney cells. Initial experimental therapeutic interventions targeting the CD40-CD40L pathway, based on CD40L antibodies, were associated with an increased incidence of thrombosis. However, this safety issue has not been observed with second-generation CD40/CD40L antibodies that have been engineered to prevent platelet activation. With these advancements, together with recent preclinical and clinical findings, it is anticipated that selective blockade of the CD40-CD40L pathway may address the unmet treatment needs in SLE, LN and other autoimmune diseases.
MeSH term(s)	Animals ; CD40 Antigens/immunology ; CD40 Ligand/immunology ; Humans ; Kidney/immunology ; Kidney/physiopathology ; Lupus Erythematosus, Systemic/immunology ; Lupus Nephritis/immunology
Chemical Substances	CD40 Antigens ; CD40 Ligand (147205-72-9)
Language	English
Publishing date	2020-09-14
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2144145-5
ISSN	1873-0183 ; 1568-9972
ISSN (online)	1873-0183
ISSN	1568-9972
DOI	10.1016/j.autrev.2020.102668
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Zs.A 5913: Show issues

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Article ; Online: Transcriptional insights into pathogenesis of cutaneous systemic sclerosis using pathway driven meta-analysis assisted by machine learning methods.

Xu, Xiao / Ramanujam, Meera / Visvanathan, Sudha / Assassi, Shervin / Liu, Zheng / Li, Li

PloS one

2020 Volume 15, Issue 11, Page(s) e0242863

Abstract: Pathophysiology of systemic sclerosis (SSc, Scleroderma), an autoimmune rheumatic disease, comprises of mechanisms that drive vasculopathy, inflammation and fibrosis. Understanding of the disease and associated clinical heterogeneity has advanced ... ...

Abstract	Pathophysiology of systemic sclerosis (SSc, Scleroderma), an autoimmune rheumatic disease, comprises of mechanisms that drive vasculopathy, inflammation and fibrosis. Understanding of the disease and associated clinical heterogeneity has advanced considerably in the past decade, highlighting the necessity of more specific targeted therapy. While many of the recent trials in SSc failed to meet the primary end points that predominantly relied on changes in modified Rodnan skin scores (MRSS), sub-group analysis, especially those focused on the basal skin transcriptomic data have provided insights into patient subsets that respond to therapies. These findings suggest that deeper understanding of the molecular changes in pathways is very important to define disease drivers in various patient subgroups. In view of these challenges, we performed meta-analysis on 9 public available SSc microarray studies using a novel pathway pivoted approach combining consensus clustering and machine learning assisted feature selection. Selected pathway modules were further explored through cluster specific topological network analysis in search of novel therapeutic concepts. In addition, we went beyond previously described SSc class divisions of 3 clusters (e.g. inflammation, fibro-proliferative, normal-like) and expanded into a much finer stratification in order to profile SSc patients more accurately. Our analysis unveiled an important 80 pathway signatures that differentiated SSc patients into 8 unique subtypes. The 5 pathway modules derived from such signature successfully defined the 8 SSc subsets and were validated by in-silico cellular deconvolution analysis. Myeloid cells and fibroblasts involvement in different clusters were confirmed and linked to corresponding pathway activities. Collectively, our findings revealed more complex disease subtypes in SSc; Key gene mediators such as IL6, FGFR1, TLR7, PLCG2, IRK2 identified by network analysis underscored the scientific rationale for exploring additional targets in treatment of SSc.
MeSH term(s)	Computational Biology ; Fibrosis/genetics ; Fibrosis/pathology ; Humans ; Interleukin-6/genetics ; Machine Learning ; Phospholipase C gamma/genetics ; Potassium Channels, Inwardly Rectifying/genetics ; Receptor, Fibroblast Growth Factor, Type 1/genetics ; Scleroderma, Systemic/genetics ; Signal Transduction/genetics ; Skin/metabolism ; Skin/pathology ; Toll-Like Receptor 7/genetics ; Transcription, Genetic ; Transcriptome/genetics
Chemical Substances	IL6 protein, human ; Interleukin-6 ; Potassium Channels, Inwardly Rectifying ; TLR7 protein, human ; Toll-Like Receptor 7 ; inward rectifier potassium channel 2 ; FGFR1 protein, human (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 1 (EC 2.7.10.1) ; PLCG2 protein, human (EC 3.1.4.3) ; Phospholipase C gamma (EC 3.1.4.3)
Language	English
Publishing date	2020-11-30
Publishing country	United States
Document type	Journal Article ; Meta-Analysis
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0242863
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Article ; Online: Transcriptional insights into pathogenesis of cutaneous systemic sclerosis using pathway driven meta-analysis assisted by machine learning methods.

Xiao Xu / Meera Ramanujam / Sudha Visvanathan / Shervin Assassi / Zheng Liu / Li Li

PLoS ONE, Vol 15, Iss 11, p e

2020 Volume 0242863

Abstract	Pathophysiology of systemic sclerosis (SSc, Scleroderma), an autoimmune rheumatic disease, comprises of mechanisms that drive vasculopathy, inflammation and fibrosis. Understanding of the disease and associated clinical heterogeneity has advanced considerably in the past decade, highlighting the necessity of more specific targeted therapy. While many of the recent trials in SSc failed to meet the primary end points that predominantly relied on changes in modified Rodnan skin scores (MRSS), sub-group analysis, especially those focused on the basal skin transcriptomic data have provided insights into patient subsets that respond to therapies. These findings suggest that deeper understanding of the molecular changes in pathways is very important to define disease drivers in various patient subgroups. In view of these challenges, we performed meta-analysis on 9 public available SSc microarray studies using a novel pathway pivoted approach combining consensus clustering and machine learning assisted feature selection. Selected pathway modules were further explored through cluster specific topological network analysis in search of novel therapeutic concepts. In addition, we went beyond previously described SSc class divisions of 3 clusters (e.g. inflammation, fibro-proliferative, normal-like) and expanded into a much finer stratification in order to profile SSc patients more accurately. Our analysis unveiled an important 80 pathway signatures that differentiated SSc patients into 8 unique subtypes. The 5 pathway modules derived from such signature successfully defined the 8 SSc subsets and were validated by in-silico cellular deconvolution analysis. Myeloid cells and fibroblasts involvement in different clusters were confirmed and linked to corresponding pathway activities. Collectively, our findings revealed more complex disease subtypes in SSc; Key gene mediators such as IL6, FGFR1, TLR7, PLCG2, IRK2 identified by network analysis underscored the scientific rationale for exploring additional targets in treatment of ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Shared and distinct mechanisms of fibrosis.

Distler, Jörg H W / Györfi, Andrea-Hermina / Ramanujam, Meera / Whitfield, Michael L / Königshoff, Melanie / Lafyatis, Robert

Nature reviews. Rheumatology

2019 Volume 15, Issue 12, Page(s) 705–730

Abstract: Fibrosis is defined as an excessive deposition of connective tissue components and can affect virtually every organ system, including the skin, lungs, liver and kidney. Fibrotic tissue remodelling often leads to organ malfunction and is commonly ... ...

Abstract	Fibrosis is defined as an excessive deposition of connective tissue components and can affect virtually every organ system, including the skin, lungs, liver and kidney. Fibrotic tissue remodelling often leads to organ malfunction and is commonly associated with high morbidity and mortality. The medical need for effective antifibrotic therapies is thus very high. However, the extraordinarily high costs of drug development and the rare incidence of many fibrotic disorders hinder the development of targeted therapies for individual fibrotic diseases. A potential strategy to overcome this challenge is to target common mechanisms and core pathways that are of central pathophysiological relevance across different fibrotic diseases. The factors influencing susceptibility to and initiation of these diseases are often distinct, with disease-specific and organ-specific risk factors, triggers and sites of first injury. Fibrotic remodelling programmes with shared fibrotic signalling responses such as transforming growth factor-β (TGFβ), platelet-derived growth factor (PDGF), WNT and hedgehog signalling drive disease progression in later stages of fibrotic diseases. The convergence towards shared responses has consequences for drug development as it might enable the development of general antifibrotic compounds that are effective across different disease entities and organs. Technological advances, including new models, single-cell technologies and gene editing, could provide new insights into the pathogenesis of fibrotic diseases and the development of drugs for their treatment.
MeSH term(s)	Animals ; Connective Tissue Diseases/drug therapy ; Connective Tissue Diseases/etiology ; Connective Tissue Diseases/metabolism ; Disease Management ; Extracellular Matrix Proteins/metabolism ; Fibrosis ; Genetic Predisposition to Disease ; Humans ; Immunity, Cellular ; Immunologic Factors/therapeutic use
Chemical Substances	Extracellular Matrix Proteins ; Immunologic Factors
Language	English
Publishing date	2019-11-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2491532-4
ISSN	1759-4804 ; 1759-4790
ISSN (online)	1759-4804
ISSN	1759-4790
DOI	10.1038/s41584-019-0322-7
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Zs.A 6338: Show issues

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Article ; Online: BTK inhibition modulates multiple immune cell populations involved in the pathogenesis of immune mediated nephritis.

Chalmers, Samantha A / Garcia, Sayra J / Webb, Deborah / Herlitz, Leal / Fine, Jay / Klein, Elliott / Ramanujam, Meera / Putterman, Chaim

Clinical immunology (Orlando, Fla.)

2020 Volume 223, Page(s) 108640

Abstract: Lupus nephritis (LN) is a serious end organ complication of systemic lupus erythematosus. Nephrotoxic serum nephritis (NTN) is an inducible model of LN, which utilizes passive transfer of pre-formed nephrotoxic antibodies to initiate disease. In previous ...

Abstract	Lupus nephritis (LN) is a serious end organ complication of systemic lupus erythematosus. Nephrotoxic serum nephritis (NTN) is an inducible model of LN, which utilizes passive transfer of pre-formed nephrotoxic antibodies to initiate disease. In previous studies, we demonstrated that the Bruton's tyrosine kinase inhibitor, BI-BTK-1, prevents the development of nephritis in NTN when treatment was started prior to nephrotoxic serum transfer, and reverses established proteinuria as well. We manipulated the initiation and duration of BI-BTK-1 therapy in NTN to study its delayed therapeutic effects when treatment is given later in the disease course, as well as to further understand what effect BI-BTK-1 is having to prevent initiation of nephritis with early treatment. Early treatment and remission induction each correlated with decreased inflammatory macrophages, CD4+ and CD8+ T cells, and decreased B220+ B cells. Additionally, an increased proportion of resident macrophages within the CD45+ population favored a delay of disease onset and remission induction. We also studied the cellular processes involved in reactivation of nephritis by withdrawing BI-BTK-1 treatment at different time points. Treatment cessation led to either early or later onset of renal flares inversely dependent on the initial duration of BTK inhibition, as assessed by increased proteinuria and BUN levels and worse renal pathology. These flares were associated with an increase in kidney CD45+ infiltrates, including myeloid cell populations. IL-6, CD14, and CCL2 were also increased in mice developing late flares. These analyses point to the role of macrophages as an important contributor to the pathogenesis of immune mediated nephritis, and further support the therapeutic potential of BTK inhibition in this disease and related conditions.
MeSH term(s)	Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors ; Animals ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Disease Models, Animal ; Humans ; Kidney/pathology ; Leukocyte Common Antigens/metabolism ; Lupus Nephritis/drug therapy ; Macrophages/immunology ; Mice ; Mice, 129 Strain ; Molecular Targeted Therapy ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Proteinuria
Chemical Substances	Protein Kinase Inhibitors ; Agammaglobulinaemia Tyrosine Kinase (EC 2.7.10.2) ; Btk protein, mouse (EC 2.7.10.2) ; Leukocyte Common Antigens (EC 3.1.3.48)
Language	English
Publishing date	2020-12-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2020.108640
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Zs.A 880: Show issues

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Article ; Online: Therapeutic targeting of macrophages in lupus nephritis.

Chalmers, Samantha A / Chitu, Violeta / Ramanujam, Meera / Putterman, Chaim

Discovery medicine

2015 Volume 20, Issue 108, Page(s) 43–49

Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease which results in multiple different end organ pathologies, including the kidney. Lupus nephritis (LN) is one of the most serious complications of SLE, and a leading cause of morbidity and ... ...

Abstract	Systemic lupus erythematosus (SLE) is an autoimmune disease which results in multiple different end organ pathologies, including the kidney. Lupus nephritis (LN) is one of the most serious complications of SLE, and a leading cause of morbidity and mortality. Current treatment options are suboptimal, involving non-specific immunosuppression which exposes patients to potentially serious side effects with no guarantee of remission. More targeted therapeutic approaches may improve treatment results. Many studies have implicated macrophages as actively contributing to LN pathogenesis in both human and murine disease. Indeed, various studies have shown that depletion of macrophage populations, inhibition of macrophage recruitment, and disruption of inflammatory macrophage activation and polarization have significantly ameliorated nephritis in several different murine LN models. The current literature explores targeting macrophages by several different means, including the CSF-1/CSF-1R signaling axis, the CX3CL1/CX3CR1 signaling axis, the CCL2/CCR2 signaling axis, and Bruton's Tyrosine Kinase (BTK), all of which hold promise as targets for future LN treatments. These studies highlight the potential benefit of targeting macrophages in LN, and emphasize the need for future investigations to discern the ideal mean(s) for targeting macrophages in LN.
MeSH term(s)	Animals ; Chemokines/immunology ; Disease Models, Animal ; Humans ; Lupus Nephritis/immunology ; Lupus Nephritis/pathology ; Lupus Nephritis/therapy ; Macrophages/immunology ; Macrophages/pathology ; Mice ; Receptors, Chemokine/immunology ; Signal Transduction/immunology
Chemical Substances	Chemokines ; Receptors, Chemokine
Language	English
Publishing date	2015-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	1944-7930
ISSN (online)	1944-7930
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A novel tetrapeptide derivative exhibits in vitro inhibition of neutrophil-derived reactive oxygen species and lysosomal enzymes release.

Miriyala, Sumitra / Panchatcharam, Manikandan / Ramanujam, Meera / Puvanakrishnan, Rengarajulu

Oxidative medicine and cellular longevity

2013 Volume 2013, Page(s) 853210

Abstract: Neutrophil infiltration plays a major role in the pathogenesis of myocardial injury. Oxidative injury is suggested to be a central mechanism of the cellular damage after acute myocardial infarction. This study is pertained to the prognostic role of a ... ...

Abstract	Neutrophil infiltration plays a major role in the pathogenesis of myocardial injury. Oxidative injury is suggested to be a central mechanism of the cellular damage after acute myocardial infarction. This study is pertained to the prognostic role of a tetrapeptide derivative PEP1261 (BOC-Lys(BOC)-Arg-Asp-Ser(tBu)-OtBU), a peptide sequence (39-42) of lactoferrin, studied in the modulation of neutrophil functions in vitro by measuring the reactive oxygen species (ROS) generation, lysosomal enzymes release, and enhanced expression of C proteins. The groundwork experimentation was concerned with the isolation of neutrophils from the normal and acute myocardial infarct rats to find out the efficacy of PEP1261 in the presence of a powerful neutrophil stimulant, phorbol 12-myristate 13 acetate (PMA). Stimulation of neutrophils with PMA resulted in an oxidative burst of superoxide anion and enhanced release of lysosomal enzymes and expression of complement proteins. The present study further demonstrated that the free radicals increase the complement factors in the neutrophils confirming the role of ROS. PEP1261 treatment significantly reduced the levels of superoxide anion and inhibited the release of lysosomal enzymes in the stimulated control and infarct rat neutrophils. This study demonstrated that PEP1261 significantly inhibited the effect on the ROS generation as well as the mRNA synthesis and expression of the complement factors in neutrophils isolated from infarct heart.
MeSH term(s)	Animals ; Complement System Proteins/metabolism ; Densitometry ; Female ; Lysosomes/drug effects ; Lysosomes/enzymology ; Myocardial Infarction/pathology ; Neutrophils/drug effects ; Neutrophils/metabolism ; Oligopeptides/chemical synthesis ; Oligopeptides/chemistry ; Oligopeptides/pharmacology ; Rats ; Rats, Wistar ; Reactive Oxygen Species/metabolism
Chemical Substances	Oligopeptides ; Reactive Oxygen Species ; Complement System Proteins (9007-36-7)
Language	English
Publishing date	2013-05-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2455981-7
ISSN	1942-0994 ; 1942-0994
ISSN (online)	1942-0994
ISSN	1942-0994
DOI	10.1155/2013/853210
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Article ; Online: IL36 is a critical upstream amplifier of neutrophilic lung inflammation in mice.

Koss, Carolin K / Wohnhaas, Christian T / Baker, Jonathan R / Tilp, Cornelia / Przibilla, Michèl / Lerner, Carmen / Frey, Silvia / Keck, Martina / Williams, Cara M M / Peter, Daniel / Ramanujam, Meera / Fine, Jay / Gantner, Florian / Thomas, Matthew / Barnes, Peter J / Donnelly, Louise E / El Kasmi, Karim C

Communications biology

2021 Volume 4, Issue 1, Page(s) 172

Abstract: IL-36, which belongs to the IL-1 superfamily, is increasingly linked to neutrophilic inflammation. Here, we combined in vivo and in vitro approaches using primary mouse and human cells, as well as, acute and chronic mouse models of lung inflammation to ... ...

Abstract	IL-36, which belongs to the IL-1 superfamily, is increasingly linked to neutrophilic inflammation. Here, we combined in vivo and in vitro approaches using primary mouse and human cells, as well as, acute and chronic mouse models of lung inflammation to provide mechanistic insight into the intercellular signaling pathways and mechanisms through which IL-36 promotes lung inflammation. IL-36 receptor deficient mice exposed to cigarette smoke or cigarette smoke and H1N1 influenza virus had attenuated lung inflammation compared with wild-type controls. We identified neutrophils as a source of IL-36 and show that IL-36 is a key upstream amplifier of lung inflammation by promoting activation of neutrophils, macrophages and fibroblasts through cooperation with GM-CSF and the viral mimic poly(I:C). Our data implicate IL-36, independent of other IL-1 family members, as a key upstream amplifier of neutrophilic lung inflammation, providing a rationale for targeting IL-36 to improve treatment of a variety of neutrophilic lung diseases.
MeSH term(s)	Animals ; Cells, Cultured ; Cigarette Smoking ; Disease Models, Animal ; Female ; Fibroblasts/immunology ; Fibroblasts/metabolism ; Humans ; Influenza A Virus, H1N1 Subtype/pathogenicity ; Interleukin-1/genetics ; Interleukin-1/metabolism ; Lung/immunology ; Lung/metabolism ; Lung/virology ; Macrophage Activation ; Macrophages, Alveolar/immunology ; Macrophages, Alveolar/metabolism ; Male ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Neutrophil Activation ; Neutrophils/immunology ; Neutrophils/metabolism ; Neutrophils/virology ; Orthomyxoviridae Infections/genetics ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/metabolism ; Orthomyxoviridae Infections/virology ; Pneumonia, Viral/genetics ; Pneumonia, Viral/immunology ; Pneumonia, Viral/metabolism ; Pneumonia, Viral/virology ; Receptors, Interleukin-1/genetics ; Receptors, Interleukin-1/metabolism ; Signal Transduction ; Mice
Chemical Substances	IL1F9 protein, mouse ; Interleukin-1 ; Receptors, Interleukin-1 ; interleukin-36 receptor, mouse
Language	English
Publishing date	2021-02-08
Publishing country	England
Document type	Journal Article
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-021-01703-3
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Article ; Online: Targeting of the immune system in systemic lupus erythematosus.

Ramanujam, Meera / Davidson, Anne

Expert reviews in molecular medicine

2008 Volume 10, Page(s) e2

Abstract: Systemic lupus erythematosus (SLE) is a complex immune disorder in which loss of tolerance to nucleic acid antigens and other crossreactive antigens is associated with the development of pathogenic autoantibodies that damage target organs, including the ... ...

Abstract	Systemic lupus erythematosus (SLE) is a complex immune disorder in which loss of tolerance to nucleic acid antigens and other crossreactive antigens is associated with the development of pathogenic autoantibodies that damage target organs, including the skin, joints, brain and kidney. New drugs based on modulation of the immune system are currently being developed for the treatment of SLE. Many of these new therapies do not globally suppress the immune system but target specific activation pathways relevant to SLE pathogenesis. Immune modulation in SLE is complicated by differences in the immune defects between patients and at different disease stages. Since both deficiency and hyperactivity of the immune system can give rise to SLE, the ultimate goal for SLE therapy is to restore homeostasis without affecting protective immune responses to pathogens. Here we review recent immunological advances that have enhanced our understanding of SLE pathogenesis and discuss how they may lead to the development of new treatment regimens.
MeSH term(s)	Animals ; Cytokines/immunology ; Cytokines/physiology ; Drug Delivery Systems ; Humans ; Immune System/drug effects ; Immune System/pathology ; Immunity, Innate/immunology ; Immunotherapy ; Lupus Erythematosus, Systemic/drug therapy ; Lupus Erythematosus, Systemic/immunology ; Lupus Erythematosus, Systemic/pathology ; Lupus Nephritis/immunology ; Lupus Nephritis/pathology ; Lymphocyte Activation/immunology ; Models, Biological
Chemical Substances	Cytokines
Language	English
Publishing date	2008-01-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	1462-3994
ISSN (online)	1462-3994
DOI	10.1017/S1462399408000562
Database	MEDical Literature Analysis and Retrieval System OnLINE

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