Inhibition of IL-11 signalling extends mammalian healthspan and lifespan.

For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark. Here we examined whether IL-11, a pro-inflammatory cytokine of the IL-6 family, has a negative effect on age-associated disease and lifespan. As mice age, IL-11 is upregulated across cell types and tissues to regulate an ERK-AMPK-mTORC1 axis to modulate cellular, tissue- and organismal-level ageing pathologies.

Targeting endogenous kidney regeneration using anti-IL11 therapy in acute and chronic models of kidney disease.

The kidney has large regenerative capacity, but this is compromised when kidney damage is excessive and renal tubular epithelial cells (TECs) undergo SNAI1-driven growth arrest. Here we investigate the role of IL11 in TECs, kidney injury and renal repair. IL11 stimulation of TECs induces ERK- and p90RSK-mediated GSK3β inactivation, SNAI1 upregulation and pro-inflammatory gene expression.

IL11 Stimulates IL33 Expression and Proinflammatory Fibroblast Activation across Tissues.

Interleukin 11 (IL11) is upregulated in inflammatory conditions, where it is mostly believed to have anti-inflammatory activity. However, recent studies suggest instead that IL11 promotes inflammation by activating fibroblasts. Here, we assessed whether IL11 is pro- or anti-inflammatory in fibroblasts.

Hepatocyte Specific gp130 Signalling Underlies APAP Induced Liver Injury.

N-acetyl-p-aminophenol (APAP)-induced liver damage is associated with upregulation of Interleukin-11 (IL11), which is thought to stimulate (gp130)-mediated STAT3 activity in hepatocytes, as a compensatory response. However, recent studies have found IL11/IL11RA/gp130 signaling to be hepatotoxic. To investigate further the role of IL11 and gp130 in APAP liver injury, we generated two new mouse strains with conditional knockout (CKO) of either (CKO) or gp130 (CKO) in adult hepatocytes.

IL11 Activates Pancreatic Stellate Cells and Causes Pancreatic Inflammation, Fibrosis and Atrophy in a Mouse Model of Pancreatitis.

Interleukin-11 (IL11) is important for fibrosis and inflammation, but its role in the pancreas is unclear. In pancreatitis, fibrosis, inflammation and organ dysfunction are associated with pancreatic stellate cell (PSC)-to-myofibroblast transformation. Here, we show that IL11 stimulation of PSCs, which specifically express IL11RA in the pancreas, results in transient STAT3 phosphorylation, sustained ERK activation and PSC activation.

Protocol of a systematic review and network meta-analysis for the prevention and treatment of perinatal depression.

Introduction: Perinatal depression is common and can often lead to adverse health outcomes for mother and child. Multiple pharmacological and non-pharmacological treatments have been evaluated against usual care or placebo controls in meta-analyses for preventing and treating perinatal depression compared. It is not yet established which of these candidate treatments might be the optimal approach for prevention or treatment.

Redefining IL11 as a regeneration-limiting hepatotoxin and therapeutic target in acetaminophen-induced liver injury.

Acetaminophen (-acetyl--aminophenol; APAP) toxicity is a common cause of liver damage. In the mouse model of APAP-induced liver injury (AILI), interleukin 11 (IL11) is highly up-regulated and administration of recombinant human IL11 (rhIL11) has been shown to be protective. Here, we demonstrate that the beneficial effect of rhIL11 in the mouse model of AILI is due to its inhibition of endogenous mouse IL11 activity.

Characterization of substrate preference for Slc1p and Cst26p in Saccharomyces cerevisiae using lipidomic approaches and an LPAAT activity assay.

Background: Phosphatidic acid (PA) is a key regulated intermediate and precursor for de novo biosynthesis of all glycerophospholipids. PA can be synthesized through the acylation of lysophosphatidic acid (LPA) by 1-acyl-3-phosphate acyltransferase (also called lysophosphatidic acid acyltransferase, LPAAT). Recent findings have substantiated the essential roles of acyltransferases in various biological functions.

Toward one step analysis of cellular lipidomes using liquid chromatography coupled with mass spectrometry: application to Saccharomyces cerevisiae and Schizosaccharomyces pombe lipidomics.

Recent rapid growth of lipidomics is mainly attributed to technological advances in mass spectrometry. Development of soft ionization techniques, in combination with computational tools, has spurred subsequent development of various methods for lipid analysis. However, none of these existing approaches can cover major cellular lipids in a single run.

A clinical monitoring system for clozapine.

Objective: To describe a framework for the initiation and ongoing monitoring of patients on clozapine, and detail support materials that can be used in clinical settings, including general practice, to support this process.

Conclusions: A framework is described. Clozapine has a special place in the management of treatment-resistant schizophrenia.

Development of clinical guidelines for the pharmacological management of behavioural disturbance and aggression in people with psychosis.

Objective: To describe the process underpinning the development of clinical guidelines for the management of behavioural disturbance in psychosis.

Method: A structured process was followed, encompassing a literature review, focus groups with key staff, and pilot testing and monitoring of the guidelines in an acute psychiatric setting.

Results: The process was well accepted by staff and was found useful in monitoring outcomes in a naturalistic setting.

The National Health Performance Framework: an evaluation model for use by psychiatrists.

Objectives: To demonstrate the use of the National Health Performance Framework as an evaluation framework for clinical interventions and service outcomes in mental health.

Conclusions: Evaluation is not a complex process. What is required is a willingness to be accountable for outcomes of care.

Partnerships between academic psychiatry and the pharmaceutical industry: the Lilly MAP Initiative.

Objective: To examine the relationship between academic psychiatry and the pharmaceutical industry, focusing on a partnership between academics in Melbourne and Eli Lilly and Company (Lilly Melbourne Academic Psychiatry).

Conclusions: Relationships between the pharmaceutical industry and the medical profession (including psychiatry) are under scrutiny as never before. Despite the complex nature of the relationship, the present paper argues that partnerships with external corporations such as pharmaceutical companies are of increasing importance for academic departments of psychiatry and research institutes, in environments in which core funding for tertiary institutes is being reduced.