Breaking News
June 19, 2018 - Study finds elevated risk of congenital defects in lithium-exposed infants
June 19, 2018 - Test-Taking Can Be Tough for Kids With Vision Problems
June 19, 2018 - Injections for knee osteoarthritis—’subtle but significant’ impact of revisions in clinical practice guidelines
June 19, 2018 - Researchers develop new approach to assess effectiveness of Men B vaccine
June 19, 2018 - Study shows link between financial literacy and hospitalization risk in older adults
June 19, 2018 - New study examines how the brain plays role in rheumatoid arthritis inflammation
June 19, 2018 - Researchers discover new defense mechanism against oxygen radicals
June 19, 2018 - WVU researcher aims to produce updated whooping cough vaccine
June 19, 2018 - Scientists develop novel computational framework to support personalized cancer treatment
June 19, 2018 - Rate of dementia on the decline—but beware of growing numbers
June 19, 2018 - Microglia play protective role in response to retinal detachment, shows study
June 19, 2018 - Technology breakthrough could enable detection of fetal genetic abnormalities in early pregnancy
June 19, 2018 - Novel chip can be used to identify rhinovirus strains as cause of asthma
June 19, 2018 - Effects of in vitro fertilization depend on genetic variation inherited from parents
June 19, 2018 - Heart attack patients unable to resume work report depression and financial hardship
June 19, 2018 - Study combines gene editing and stem cell technologies to predict person’s risk for heart disease
June 19, 2018 - Weight loss of 20% or greater results in better outcomes for overweight, obese adults with knee osteoarthritis
June 19, 2018 - Alnylam Reports Updated Positive Results from Phase 1/2 Study of Lumasiran in Patients with Primary Hyperoxaluria Type 1 (PH1)
June 19, 2018 - Study predicts most people with earliest Alzheimer’s signs won’t develop dementia associated with the disease
June 19, 2018 - Abnormal sleep duration linked to metabolic syndrome in new study
June 19, 2018 - Researchers develop new method to preserve fertility in boys with prepubertal cancer
June 19, 2018 - Late onset of diabetes could be indicative of pancreatic cancer
June 19, 2018 - WHO releases new International Classification of Diseases (ICD-11)
June 19, 2018 - Skin tone makes big difference in diagnosis and treatment of dermatologic conditions
June 19, 2018 - After addiction, the long road back to good health
June 19, 2018 - High blood pressure could be an early sign of dementia
June 19, 2018 - Innovative drugs and new European treatment guidelines refine, improve MS therapy
June 19, 2018 - BIDMC scientists develop new tool to benefit patients with HCV-associated liver failure
June 19, 2018 - Diabetes diagnosis may come with increased risk of pancreatic cancer for African-Americans, Latinos
June 19, 2018 - Personalized Goals, Cash Motivate Heart Patients to Exercise
June 19, 2018 - Nipah Virus (NiV) | CDC
June 19, 2018 - Genomics offers new treatment options for infants with range of soft tissue tumors
June 18, 2018 - Study shows how moderate consumption of alcohol can protect the heart
June 18, 2018 - Gene editing technology predicts heart disease risk
June 18, 2018 - Who Will and Who Won’t Get the Flu?
June 18, 2018 - Research shows effective responses to online feedback
June 18, 2018 - Scientists to focus on big data and genetics to identify risk factors for dementia
June 18, 2018 - Ultrasound-based technology for assessing overweight adolescents with liver disease
June 18, 2018 - Osteochondral knee defect treated using cell technology
June 18, 2018 - New clinical trial finds no evidence to support use of tamsulosin for kidney stones
June 18, 2018 - Study demonstrates increased levels of gum disease in people at risk of rheumatoid arthritis
June 18, 2018 - Ebola & Marburg | NIH: National Institute of Allergy and Infectious Diseases
June 18, 2018 - Brains, eyes, testes: off-limits for transplants?
June 18, 2018 - Drug used to treat myelofibrosis can awaken ‘dormant’ lymphomas in the bone marrow
June 18, 2018 - New study focuses on best, cost effective practices to bridge treatment gap for brain disorders
June 18, 2018 - New study highlights predictors that prevent from achieving remission in early RA
June 18, 2018 - Neuroscientists map feeling of cool touch to the brain’s insula in mouse model
June 18, 2018 - Study highlights potential use of blood biomarkers as diagnostic tool for sleep apnea
June 18, 2018 - Eating plant-based diet can reduce risk for heart problems in people with type 2 diabetes
June 18, 2018 - Lenabasum has acceptable safety and tolerability in diffuse cutaneous systemic sclerosis
June 18, 2018 - Study shows link between risky opioid prescriptions and increased odds of death
June 18, 2018 - Bone density scans could help determine likelihood of cardiovascular disease
June 18, 2018 - Mechanical thrombectomy appears to be important therapy for acute stroke in very old patients
June 18, 2018 - Novel compound as effective as FDA-approved antibiotics for treating deadly infections
June 18, 2018 - Ironwood Pharmaceuticals Announces FDA Orphan Drug Designation for Olinciguat for the Treatment of Sickle Cell Disease
June 18, 2018 - Surgical outcomes equivalent whether physician anesthesiologist assisted by nurse anesthetist or AA
June 18, 2018 - Studies provide insight into molecular changes prior to onset of arthritis
June 18, 2018 - Dyaco unveils specialist medical and rehabilitation equipment range in the UK
June 18, 2018 - Engineers develop algorithm to monitor joints of patients with arthritis
June 18, 2018 - Women with higher vitamin D blood levels have lower risk for breast cancer
June 18, 2018 - New studies help elucidate role of sleep in chronic pain
June 18, 2018 - Researchers link red meat sensitivity spread by ticks with heart disease
June 18, 2018 - Research explores role of autopsy in cardiovascular medicine
June 18, 2018 - Motif Bio Submits NDA for Iclaprim
June 18, 2018 - NIH-funded researchers identify target for chikungunya treatment
June 18, 2018 - Negative emotions are murkier, less distinct in adolescence
June 18, 2018 - Gut microbiome may be potential contributor to depression, anxiety in people with obesity
June 18, 2018 - Canakinumab reduces gout rate by more than half in atherosclerosis patients, study shows
June 18, 2018 - What Does the Future Hold?
June 18, 2018 - FDA Approves Keytruda (pembrolizumab) for Treatment of Refractory or Relapsed Primary Mediastinal Large B-Cell Lymphoma (PMBCL)
June 18, 2018 - School cliques don’t always click
June 18, 2018 - Three experts from The Tinnitus Clinic contribute to major review on pulsatile tinnitus
June 18, 2018 - Unwieldy health costs often stand between teachers and fatter paychecks
June 18, 2018 - Link between frailty and mortality remains unchanged despite lower death rates, study finds
June 18, 2018 - Sleep disorders appear to be first sign of serious neurological diseases
June 18, 2018 - Childhood, adult obesity raise risk of developing hip and knee osteoarthritis
June 18, 2018 - Study unravels ‘blood stem cell niche’ puzzle
June 18, 2018 - People with heart problems do not take enough exercise, shows study
June 18, 2018 - Strong Link Identified Between T2DM and Parkinson’s Disease
June 18, 2018 - Early childhood interventions show mixed results on child development
Scientists discover treatment target for sepsis

Scientists discover treatment target for sepsis

image_pdfDownload PDFimage_print

In a study published in Nature Communications, Northwestern Medicine scientists demonstrated the key role a molecule called oxPAPC plays in regulating the inflammatory response—findings which could inform the development of new therapies for the body’s life-threatening response to serious infections.

Lan Chu, a sixth-year doctoral student in Feinberg’s Driskill Graduate Program in Life Sciences (DGP), was the first author of the study.

Sepsis is a serious medical condition caused by the body’s harmful, systemic response to an infection. Inflammatory chemicals released into the bloodstream to fight the infection can lead to blood clotting, tissue damage, organ failure and death.

“Sepsis is a major health issue, with very high mortality. But we don’t really have a therapy to treat it right now,” explained principal investigator Christian Stehlik, Ph.D., the John P. Gallagher Research Professor of Rheumatology.

A common cause of sepsis is a type of bacteria called gram-negative bacteria. Immune cells in the body recognize lipopolysaccharide (LPS)—a major component of the membrane of these bacteria—which in turn triggers the potent inflammatory response.

Previously, it was understood that TLR4, a protein on the surface of immune cells, was responsible for recognizing LPS. But clinical trials of therapies targeting the TLR4 protein as a treatment for sepsis had been largely unsuccessful.

More recently, scientists discovered that immune cells actually have a second additional receptor for LPS: an intracellular protein called caspase-11 (in mice, or caspase-4 and caspase-5 in humans).

Caspase-11 binds to LPS and activates what’s known as a non-canonical inflammasome response, which plays a role in sepsis. Controlling caspase-11 could thus be a novel strategy to preventing the inflammatory overreaction seen in sepsis.

But until now, it was not understood how the caspase-11 molecule is regulated.

In the current study, the scientists discovered that a phospholipid called oxPAPC regulates caspase-11 in human and animal macrophages. The molecule does so by competing with LPS to bind to caspase-11. “If there’s enough oxPAPC, LPS cannot bind, and the excessive inflammatory response is prevented,” explained Stehlik, also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

In the study, the scientists also demonstrated that when oxPAPC is injected into mice who are then challenged with LPS, septic shock was prevented.

“Our work provides the first evidence for a negative regulator of non-canonical inflammasomes, and thus provides a basis for novel therapies targeting inflammasomes and inflammation-induced diseases,” Chu said.

In the future, for example, synthetic versions of oxPAPC—or molecules that mimic its role—could potentially be administrated to septic patients as therapy, which might temper the inflammatory response.

“At least in mice so far, oxPAPC seems to be really effective at preventing death. What we hope is that, by extension, this could also be used as a therapy for patients in the future,” Stehlik said.

In ongoing studies, Stehlik laboratory is now investigating how oxPAC is taken up by macrophages and what receptors might be involved in that process.


Explore further:
New insights into protein’s role in inflammatory response

More information:
Lan H. Chu et al. The oxidized phospholipid oxPAPC protects from septic shock by targeting the non-canonical inflammasome in macrophages, Nature Communications (2018). DOI: 10.1038/s41467-018-03409-3

Journal reference:
Nature Communications

Provided by:
Northwestern University

Tagged with:

About author

Related Articles