Pleiotropy and Specificity: Insights from the Interleukin 6 Family of Cytokines

Murakami, Masaaki; Kamimura, Daisuke; Hirano, Toshio

doi:10.1016/j.immuni.2019.03.027

Cited by 372 publications

(341 citation statements)

References 279 publications

Supporting

Mentioning

318

Contrasting

Unclassified

Order By: Relevance

“…Therefore, blockade of IL‐6 attenuates the inflammatory responses in AS. IL‐6 contains several elements for binding of transcriptional factors, including AP‐1, NF‐КB and Camo‐responsive elements, and NF‐КB plays a crucial role in the induction of IL6 transcription . In this study, we observed that the expression of IL‐6 in exosomes was significantly increased after activation of CD137 signalling.…”

Section: Discussionmentioning

confidence: 59%

Exosome derived from CD137‐modified endothelial cells regulates the Th17 responses in atherosclerosis

Geng

Zang

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

| 4659 wileyonlinelibrary.com/journal/jcmm 1 | INTRODUC TI ON T helpers 17 (Th17) cells have been identified as a new subset of lymphocytes which are shown to promote atherosclerosis (AS), and their associated cytokines in the pathogenesis of AS appear to be contradictory at first glance. 1-3 Recently, growing attention has been paid to the relative contribution of the local vs. peripheral inflammation to the procession of AS. Here, we focused on the communication between peripheral inflammation and vascular inflammation of Th17 cell differentiation during AS.Exosomes are a subset of extracellular vesicles (EVs) released by almost all types of cells, and they play a significant role in cellular proliferation, apoptosis, stress response and differentiation in the initial stage and development of AS. 4,5 In the present study, we investigated exosome-mediated cell-to-cell communication, which induced Th17 cell differentiation and promoted progression of the atherosclerotic plaque. AbstractThe role of exosomes derived from endothelial cells (ECs) in the progression of atherosclerosis (AS) and inflammation remains largely unexplored. We aimed to investigate whether exosome derived from CD137-modified ECs (CD137-Exo) played a major role in AS and to elucidate the potential mechanism underlying the inflammatory effect. Exosomes derived from mouse brain microvascular ECs treated with agonist anti-CD137 antibody were used to explore the effect of CD137 signalling in AS and inflammation in vitro and vivo. CD137-Exo efficiently induced the progression of AS in ApoE −/− mice. CD137-Exo increased the proportion of Th17 cells both in vitro and vivo. The IL-6 contained in CD137-Exo which is regulated by Akt and NF-КB pathway was verified to activate Th17 cell differentiation. IL-17 increased apoptosis, inhibited cell viability and improved lactate dehydrogenase (LDH) release in ECs subjected to inflammation induced by lipopolysaccharide (LPS). The expression of soluble intercellular adhesion molecule1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1) and E-selectin in the supernatants of ECs after IL-17 treatment was dramatically increased. CD137-Exo promoted the progression of AS and Th17 cell differentiation via NF-КB pathway mediated IL-6 expression. This finding provided a potential method to prevent local and peripheral inflammation in AS. K E Y W O R D S atherosclerosis, endothelial cells; Th17 cells, exosomes

show abstract

Section: Discussionmentioning

confidence: 59%

Exosome derived from CD137‐modified endothelial cells regulates the Th17 responses in atherosclerosis

Geng

Zang

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Increasingly, inflammatory markers such as IL-6, largely thought to be pro-inflammatory, has been shown to be pleiotropic in nature and may even have anti-inflammatory properties (176). Furthermore, individual differences in the expression and regulation of these inflammatory markers is complex and may lead to different behavioral effects (177,178).…”

Section: Inflammation and Negative Symptoms: Future Directionsmentioning

confidence: 99%

Inflammation and Negative Symptoms of Schizophrenia: Implications for Reward Processing and Motivational Deficits

Goldsmith

Rapaport

2020

Front. Psychiatry

View full text Add to dashboard Cite

Negative symptoms of schizophrenia are debilitating and chronic in nature, are difficult to treat, and contribute to poor functional outcomes. Motivational deficits are a core negative symptom and may involve alterations in reward processing, which involve subcortical regions such as the basal ganglia. More specifically, dopamine-rich regions like the ventral striatum, have been implicated in these reward-processing deficits. Inflammation is one mechanism that may underlie negative symptoms, and specifically motivational deficits, via the effects of inflammatory cytokines on the basal ganglia. Previous work has demonstrated that inflammatory stimuli decrease neural activity in the ventral striatum and decrease connectivity in reward-relevant neural circuitry. The immune system has been shown to be involved in the pathophysiology of schizophrenia, and inflammatory cytokines have been shown to be altered in patients with the disorder. This paper reviews the literature on associations between inflammatory markers and negative symptoms of schizophrenia as well as the role of anti-inflammatory drugs to target negative symptoms. We also review the literature on the role of inflammation and reward processing deficits in both healthy controls and individuals with depression. We use the literature on inflammation and depression as a basis for a model that explores potential mechanisms responsible for inflammation modulating certain aspects of negative symptoms in patients with schizophrenia. This approach may offer novel targets to treat these symptoms of the disorder that are significant barriers to functional recovery and do not respond well to available antipsychotic medications.

show abstract

“…The IL‐6 family of cytokines includes IL‐6, IL‐11, IL‐27, oncostatin M (OSM), leukaemia inhibitory factor (LIF), cardiotrophin‐1, cardiotrophin‐like cytokine (CLCF), and ciliary neurotrophic factor (CNTF; Murakami, Kamimura, & Hirano, ; Rose‐John, ). These cytokines have traditionally been grouped together as they all signal via the ubiquitously expressed signalling receptor subunit glycoprotein 130 kDa (gp130).…”

Section: Il‐11 Is An Il‐6 Family Cytokine With Distinct Biological Fumentioning

confidence: 99%

“…The IL-6 family of cytokines includes IL-6, IL-11, IL-27, oncostatin M (OSM), leukaemia inhibitory factor (LIF), cardiotrophin-1, F I G U R E 1 Overview of heart and kidney diseases defined by fibrosis and the consequent effects on organ function cardiotrophin-like cytokine (CLCF), and ciliary neurotrophic factor (CNTF; Murakami, Kamimura, & Hirano, 2019;Rose-John, 2018).…”

Section: Il-11 Is An Il-6 Family Cytokine With Distinct Biological mentioning

confidence: 99%

IL‐11 in cardiac and renal fibrosis: Late to the party but a central player

Corden

Adami

Sweeney

et al. 2020

British J Pharmacology

View full text Add to dashboard Cite

Fibrosis is a pathophysiological hallmark of cardiorenal disease. In the heart, fibrosis leads to contractile dysfunction and arrhythmias; in the kidney, it is the final common pathway for many diseases and predicts end‐stage renal failure. Despite this, there are currently no specific anti‐fibrotic treatments available for cardiac or renal disease. Recently and unexpectedly, IL‐11 was found to be of major importance for cardiorenal fibroblast activation and fibrosis. In mouse models, IL‐11 overexpression caused fibrosis of the heart and kidney while genetic deletion of Il11ra1 protected against fibrosis and preserved organ function. Neutralizing antibodies against IL‐11 or IL‐11RA have been developed that have anti‐fibrotic activity in human fibroblasts and protect against fibrosis in murine models of disease. While IL‐11 biology has been little studied and, we suggest, largely misunderstood, its autocrine activity in myofibroblasts appears non‐redundant for fibrosis, which offers new opportunities to better understand and potentially target cardiorenal fibrosis.

show abstract

Pleiotropy and Specificity: Insights from the Interleukin 6 Family of Cytokines

Cited by 372 publications

References 279 publications

Exosome derived from CD137‐modified endothelial cells regulates the Th17 responses in atherosclerosis

Exosome derived from CD137‐modified endothelial cells regulates the Th17 responses in atherosclerosis

Inflammation and Negative Symptoms of Schizophrenia: Implications for Reward Processing and Motivational Deficits

IL‐11 in cardiac and renal fibrosis: Late to the party but a central player

Contact Info

Product

Resources

About