scholarly journals Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation

2020 ◽  
Vol 71 (1) ◽  
pp. 263-276 ◽  
Author(s):  
Stuart A. Cook ◽  
Sebastian Schafer
Keyword(s):  
Tissue Regeneration ◽  
Inflammatory Diseases ◽  
Parenchymal Cell ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Cell Dysfunction ◽  
Tissue Integrity ◽  
Polarized Cells ◽  
Inflammatory Bowel ◽  
Interleukin 11

Interleukin (IL)-11 is upregulated in a wide variety of fibro-inflammatory diseases such as systemic sclerosis, rheumatoid arthritis, pulmonary fibrosis, inflammatory bowel disease, kidney disease, drug-induced liver injury, and nonalcoholic steatohepatitis. IL-11 is a member of the IL-6 cytokine family and has several distinct properties that define its unique and nonredundant roles in disease. The IL-11 receptor is highly expressed on stromal, epithelial and polarized cells, where noncanonical IL-11 signaling drives the three pathologies common to all fibro-inflammatory diseases—myofibroblast activation, parenchymal cell dysfunction, and inflammation—while also inhibiting tissue regeneration. This cytokine has been little studied, and publications on IL-11 peaked in the early 1990s, when it was largely misunderstood. Here we describe recent advances in our understanding of IL-11 biology, outline how misconceptions as to its function came about, and highlight the large potential of therapies targeting IL-11 signaling for treating human disease.

scholarly journals Opportunities and challenges in the wider adoption of liver and interconnected microphysiological systems

2017 ◽  
Vol 242 (16) ◽  
pp. 1593-1604 ◽  
Author(s):  
David J Hughes ◽  
Tomasz Kostrzewski ◽  
Emma L Sceats
Keyword(s):  
Parenchymal Cell ◽  
Pharmaceutical Research ◽  
Hepatic Function ◽  
In Vitro Models ◽  
System Level ◽  
Primary Hepatocytes ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Microphysiological Systems

Liver disease represents a growing global health burden. The development of in vitro liver models which allow the study of disease and the prediction of metabolism and drug-induced liver injury in humans remains a challenge. The maintenance of functional primary hepatocytes cultures, the parenchymal cell of the liver, has historically been difficult with dedifferentiation and the consequent loss of hepatic function limiting utility. The desire for longer term functional liver cultures sparked the development of numerous systems, including collagen sandwiches, spheroids, micropatterned co-cultures and liver microphysiological systems. This review will focus on liver microphysiological systems, often referred to as liver-on-a-chip, and broaden to include platforms with interconnected microphysiological systems or multi-organ-chips. The interconnection of microphysiological systems presents the opportunity to explore system level effects, investigate organ cross talk, and address questions which were previously the preserve of animal experimentation. As a field, microphysiological systems have reached a level of maturity suitable for commercialization and consequent evaluation by a wider community of users, in academia and the pharmaceutical industry. Here scientific, operational, and organizational considerations relevant to the wider adoption of microphysiological systems will be discussed. Applications in which microphysiological systems might offer unique scientific insights or enable studies currently feasible only with animal models are described, and challenges which might be addressed to enable wider adoption of the technologies are highlighted. A path forward which envisions the development of microphysiological systems in partnerships between academia, vendors and industry, is proposed. Impact statement Microphysiological systems are in vitro models of human tissues and organs. These systems have advanced rapidly in recent years and are now being commercialized. To achieve wide adoption in the biological and pharmaceutical research communities, microphysiological systems must provide unique insights which translate to humans. This will be achieved by identifying key applications and making microphysiological systems intuitive to use.

scholarly journals The hypoxia-adenosine link during inflammation

2017 ◽  
Vol 123 (5) ◽  
pp. 1303-1320 ◽  
Author(s):  
Jessica L. Bowser ◽  
Jae W. Lee ◽  
Xiaoyi Yuan ◽  
Holger K. Eltzschig
Keyword(s):  
Myocardial Injury ◽  
Inflammatory Diseases ◽  
Extracellular Adenosine ◽  
Tissue Integrity ◽  
The Past ◽  
Hypoxic Conditions ◽  
Inflammatory Conditions ◽  
Proinflammatory Responses ◽  
Inflammatory Bowel ◽  
The Relationship

Hypoxic tissue conditions occur during a number of inflammatory diseases and are associated with the breakdown of barriers and induction of proinflammatory responses. At the same time, hypoxia is also known to induce several adaptive and tissue-protective pathways that dampen inflammation and protect tissue integrity. Hypoxia-inducible factors (HIFs) that are stabilized during inflammatory or hypoxic conditions are at the center of mediating these responses. In the past decade, several genes regulating extracellular adenosine metabolism and signaling have been identified as being direct targets of HIFs. Here, we discuss the relationship between inflammation, hypoxia, and adenosine and that HIF-driven adenosine metabolism and signaling is essential in providing tissue protection during inflammatory conditions, including myocardial injury, inflammatory bowel disease, and acute lung injury. We also discuss how the hypoxia-adenosine link can be targeted therapeutically in patients as a future treatment approach for inflammatory diseases.

scholarly journals A20 and ABIN-1 synergistically preserve intestinal epithelial cell survival

2018 ◽  
Vol 215 (7) ◽  
pp. 1839-1852 ◽  
Author(s):  
Michael G. Kattah ◽  
Ling Shao ◽  
Yenny Y. Rosli ◽  
Hiromichi Shimizu ◽  
Michael I. Whang ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
Kinase Activity ◽  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Intestinal Epithelial ◽  
Tissue Integrity ◽  
Caspase Inhibition ◽  
Inflammatory Bowel

A20 (TNFAIP3) and ABIN-1 (TNIP1) are candidate susceptibility genes for inflammatory bowel disease and other autoimmune or inflammatory diseases, but it is unclear how these proteins interact in vivo to prevent disease. Here we show that intestinal epithelial cell (IEC)-specific deletion of either A20 or ABIN-1 alone leads to negligible IEC loss, whereas simultaneous deletion of both A20 and ABIN-1 leads to rapid IEC death and mouse lethality. Deletion of both A20 and ABIN-1 from enteroids causes spontaneous cell death in the absence of microbes or hematopoietic cells. Studies with enteroids reveal that A20 and ABIN-1 synergistically restrict death by inhibiting TNF-induced caspase 8 activation and RIPK1 kinase activity. Inhibition of RIPK1 kinase activity alone, or caspase inhibition combined with RIPK3 deletion, abrogates IEC death by blocking both apoptosis and necroptosis in A20 and ABIN-1 double-deficient cells. These data show that the disease susceptibility proteins A20 and ABIN-1 synergistically prevent intestinal inflammation by restricting IEC death and preserving tissue integrity.

scholarly journals Cholestatic Hepatitis with Small Duct Injury Associated with Celecoxib

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Suresh Kumar Nayudu ◽  
Shanti Badipatla ◽  
Masooma Niazi ◽  
Bhavna Balar
Keyword(s):  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Rare Complication ◽  
Imaging Studies ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Inflammatory Bowel ◽  
Inflammatory Drugs ◽  
Cyclooxygenase 2 Inhibitors ◽  
Metabolic Liver Diseases

Drug-induced liver injury (DILI) is a common clinical entity but is underreported due to various reasons. Cyclooxygenase-2 inhibitors like Celecoxib have been proven to be associated with lesser incidence of adverse drug reactions compared to other nonsteroidal anti-inflammatory drugs (NSAID). However, Celecoxib has been rarely reported to be associated with cholestasis and hepatitis. We present a young Hispanic female presented with cholestatic liver chemistries who has been taking Celecoxib for 3 weeks. Extensive workup did not support diagnosis of viral, autoimmune, or metabolic liver diseases. Liver biopsy revealed findings suggestive of secondary sclerosing cholangitis. Imaging studies were negative for large duct involvement, and endoscopy ruled out inflammatory bowel disease. Liver chemistries normalized after cessation of medication. We recommend that physician should be aware of this rare complication when prescribing Celecoxib.

scholarly journals Vedolizumab-Induced Liver Injury

2020 ◽  
pp. 1-6
Author(s):  
Miguel Mascarenhas Saraiva ◽  
Tiago Ribeiro ◽  
Emanuel Dias ◽  
Joanne Lopes Lopes ◽  
Hélder Cardoso ◽  
...  
Keyword(s):  
Liver Injury ◽  
Low Dose ◽  
Complete Recovery ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Post Marketing ◽  
Inflammatory Bowel ◽  
Immunomodulatory Therapies ◽  
Liver Tests ◽  
Probable Relation

Drug-induced liver injury is an important cause of acute liver injury. Immunomodulatory therapies, such as vedolizumab (VDZ), are being increasingly used for the treatment of several diseases, most importantly inflammatory bowel disease. Several studies have demonstrated the safety of this substance. To date, only one post-marketing study has reported a case of hepatotoxicity attributable to VDZ. The authors present the case of a 41-year-old woman followed at the gastroenterology outpatient clinic for ulcerative colitis (UC) and autoimmune hepatitis (AIH). This patient was being treated with low-dose glucocorticoids for AIH (prednisolone 10 mg), with adequate disease control. Additionally, she was being treated with oral salicylates (mesalamine 3 g/day) and oral budesonide (9 mg/day) for her UC. For uncontrolled UC, she was started on VDZ. Two weeks after the first infusion of VDZ, the patient developed a clinical and analytical phenotype compatible with acute hepatitis. Diagnostic workup for causes of hepatocellular liver injury retrieved no results. A liver biopsy corroborated the diagnosis of toxic hepatitis overlapping chronic liver disease. VDZ was withdrawn and the patient experienced complete recovery of liver tests over the following weeks. In this case report, we present the first post-marketing case of hepatocellular liver injury in probable relation to VDZ.

scholarly journals Drug-induced liver injury in inflammatory bowel disease: 1-year prospective observational study

2017 ◽  
Vol 23 (22) ◽  
pp. 4102 ◽  
Author(s):  
Tomas Koller ◽  
Martina Galambosova ◽  
Simona Filakovska ◽  
Michaela Kubincova ◽  
Tibor Hlavaty ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Liver Injury ◽  
Observational Study ◽  
Bowel Disease ◽  
Prospective Observational Study ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Inflammatory Bowel

Leberschaden unter oraler Antikoagulation, Statin- und ACE-Hemmertherapie

Praxis ◽  
2010 ◽  
Vol 99 (21) ◽  
pp. 1259-1265 ◽  
Author(s):  
Bruggisser ◽  
Terraciano ◽  
Rätz Bravo ◽  
Haschke
Keyword(s):  
Liver Injury ◽  
Wird Eine ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Ein 71-jähriger Patient stellt sich mit Epistaxis und ikterischen Skleren auf der Notfallstation vor. Der Patient steht unter einer Therapie mit Phenprocoumon, Atorvastatin und Perindopril. Anamnestisch besteht ein langjähriger Alkoholabusus. Laborchemisch werden massiv erhöhte Leberwerte (ALAT, Bilirubin) gesehen. Der INR ist unter oraler Antikoagulation und bei akuter Leberinsuffizienz >12. Die weiterführenden Abklärungen schliessen eine Virushepatitis und eine Autoimmunhepatitis aus. Nachdem eine Leberbiopsie durchgeführt werden kann, wird eine medikamentös-toxische Hepatitis, ausgelöst durch die Komedikation von Atorvastatin, Phenprocoumon und Perindopril bei durch Alkohol bereits vorgeschädigter Leber diagnostiziert. Epidemiologie, Pathophysiologie und Klink der medikamentös induzierten Leberschäden (drug induced liver injury, DILI), speziell von Coumarinen, Statinen und ACE-Hemmern werden im Anschluss an den Fallbericht diskutiert.

Sign in / Sign up

Export Citation Format

Share Document