Breaking News
October 20, 2018 - Antidepressant treatment may lead to improvements in sleep quality of patients with depression
October 20, 2018 - Study reports increased risk of death in children with inflammatory bowel disease
October 20, 2018 - Number of Autism Genes Now Tops 100
October 20, 2018 - Total diet replacement programmes are effective for treating obesity
October 20, 2018 - CLARIOstar used for fluorescence measurements on CSIRO’s purpose-built research vessel
October 20, 2018 - People with more copies of AMY1 gene digest starchy carbohydrates faster
October 20, 2018 - Case Comprehensive Cancer Center wins NIH grant to study health disparities
October 20, 2018 - Newly discovered compound shows potential for treating Parkinson’s disease
October 20, 2018 - High rate of non-adherence to hormonal therapy found among premenopausal early breast cancer patients
October 20, 2018 - Immunotherapy medicine found to be effective in treating uveitis
October 20, 2018 - The Pistoia Alliance Calls for Greater Collaboration to Realise Benefits of Innovation and Announces Winners of the 2018 President’s Startup Challenge
October 20, 2018 - Female internists consistently earn less than men
October 20, 2018 - Stanford team looks at dangers of teens’ vaping habits
October 20, 2018 - New approach to understanding cancers will accelerate development of better treatments
October 20, 2018 - LJI and UC San Diego awarded $ 4.5 million as part of NCI’s Cancer Moonshot initiative
October 20, 2018 - School-based HPV vaccination did not increase risky sexual behaviors among adolescent girls
October 20, 2018 - Eye discovery to pave way for more successful corneal transplants
October 20, 2018 - New analysis examines the importance of location in the opioid crisis
October 20, 2018 - Green filters increase reading speed for children with dyslexia
October 19, 2018 - Bariatric Sx Cuts Macrovascular Complications in Obesity, T2DM
October 19, 2018 - Better assessments for early age-related macular degeneration
October 19, 2018 - Visible and valued: Stanford Medicine’s first-ever LGBTQ+ Forum | News Center
October 19, 2018 - Understanding of metal-free enzymes used by bacteria could lead to new effective antibiotics
October 19, 2018 - Beckman Coulter Life Sciences announces new research-focused website
October 19, 2018 - Study finds link between refined soluble fibers, gut microbiota and liver cancer
October 19, 2018 - Social media reduces risk of depression among seniors with pain
October 19, 2018 - Newly developed synthetic DNA molecule may one day be used as ‘vaccine’ for prostate cancer
October 19, 2018 - Preoperative weight loss may not provide health benefits after surgery
October 19, 2018 - U.S. Birth Rates Continue to Drop as Age of New Moms Rises
October 19, 2018 - New technology can keep an eye on babies’ movements in the womb
October 19, 2018 - Juul e-cigarettes pose addiction risk for young users | News Center
October 19, 2018 - Gene sequencing reveals crucial molecular aspects of Trypanosoma brucei
October 19, 2018 - New DNA vaccine strategy protects mice against lethal challenge by multiple H3N2 viruses
October 19, 2018 - Study shows close link between cytokine interleukin-1ß and obesity-promoted colon cancer
October 19, 2018 - Muscle mass plays a critical role in health, shows research
October 19, 2018 - Study finds undiagnosed prediabetes in many infertile men
October 19, 2018 - The Current issue of “The view from here” is concerned with Nanotherapeutic strategies
October 19, 2018 - Delay in replacing the Pap smear with HPV screening is costing lives
October 19, 2018 - Physicians battle pediatric diseases of ear, nose, throat in Zimbabwe | News Center
October 19, 2018 - Researchers investigate why some cancers affect only young women
October 19, 2018 - Drugmakers funnel millions to lawmakers; a few dozen get $100,000-plus
October 19, 2018 - Unselfish people tend to have more children and receive higher salaries
October 19, 2018 - New findings reveal potential cellular players in tumor microenvironment
October 19, 2018 - Some countries take more time for reimbursement decisions on new cancer drugs
October 19, 2018 - Human brain cell transplant offers insights into neurological conditions
October 19, 2018 - Parental education associated with increased family health care spending
October 19, 2018 - New statistical method estimates long- and short-term risk of recurrence of breast cancer in US women
October 19, 2018 - Father’s exposure to nicotine may cause cognitive deficits in descendants
October 19, 2018 - Could we prevent Alzheimer’s disease by treating herpes?
October 19, 2018 - Nurse-led care can be more successful in managing gout
October 19, 2018 - Trump administration, pharma exchange verbal volleys on drug-price transparency
October 19, 2018 - Duke researchers find way to detect blood doping in athletes
October 19, 2018 - Many primary care doctors are still prescribing sedative drugs for older adults
October 19, 2018 - Finger length can predict sexuality in women say researchers
October 19, 2018 - Study finds differences in side-effects experienced by male and female OG cancer patients
October 19, 2018 - Dysfunction of single gene leads to miscarriages
October 19, 2018 - Few Seniors Who Self-Harm Referred for Mental Health Care
October 19, 2018 - Don’t sweat the sweet stuff
October 19, 2018 - URMC researchers discover new approach to deliver therapeutics to the brain
October 19, 2018 - Speech Pathology Australia raises awareness about Developmental Language Disorder
October 19, 2018 - Middlemen suppliers can increase drug prices and hospital bills, say Johns Hopkins researchers
October 19, 2018 - Survey finds high prevalence of HTLV-1 infection among teens and adults in Gabon
October 19, 2018 - Bliss funds research to find whether parental touch can help alleviate pain in premature infants
October 19, 2018 - Human neurons employ highly compartmentalized signaling, study shows
October 19, 2018 - Ultromics expands multiple clinical trials for coronary heart disease to the U.S.
October 19, 2018 - $11 million NIH grant for Clemson University helps launch new center for musculoskeletal research
October 19, 2018 - A new approach identified to control Zika virus, dengue fever
October 19, 2018 - Head Blows Without Concussion May Not Damage Brain, Study Claims
October 19, 2018 - US opioid use not declined, despite focus on abuse and awareness of risk
October 19, 2018 - Next-generation RNA sequencing technology sheds new light on human mitochondrial diseases
October 19, 2018 - UT Southwestern biochemist receives 2019 Breakthrough Prize in Life Sciences for innate immunity discovery
October 19, 2018 - The immune system also plays a key role in day-to-day function of healthy organs
October 19, 2018 - New tool may reveal how the brain structure impacts brain activity, human behavior
October 19, 2018 - Trump Administration announces ‘Winning on Reducing Food Waste’ initiative
October 19, 2018 - For-profit nursing home residents more likely to experience health issues caused by substandard care
October 19, 2018 - Incidence of stroke has risen steadily among marijuana users, show studies
October 19, 2018 - Conceptual framework proposed to examine role of exercise in multiple sclerosis
October 19, 2018 - Near infrared spectroscopy technique for accurate evaluation of chondral injuries
October 19, 2018 - Scientists receive $5.1 million grant to develop stem cell-based therapy for blinding retinal conditions
October 19, 2018 - Shorter physician encounters associated with antibiotic prescribing
UCR-led research discovers that human protein could be used to treat sepsis

UCR-led research discovers that human protein could be used to treat sepsis

image_pdfDownload PDFimage_print

A research team led by a biomedical scientist at the University of California, Riverside has discovered that the human protein resistin could be used to treat sepsis, the body’s extreme and uncontrolled immune response to an infection.

Sepsis kills about one in five affected people. Without timely treatment, this medical emergency can rapidly damage tissue and lead to organ failure. Using a transgenic mouse model expressing this hormone, the researchers found that mice expressing resistin had a 100 percent survival rate from a sepsis-like infection when compared to wild-type mice with the same infection.

“A lot of scientific literature has posited that resistin is harmful,” said Meera G. Nair, an assistant professor of biomedical sciences at UCR’s School of Medicine and lead author of the paper that appears in Proceedings of the National Academy of Sciences. “But we may have misunderstood this secreted protein in our blood. My lab was intrigued by why we make so much of a substance that is, supposedly, not good for us. Resistin, we have now found, has a benefit: it is protective in sepsis. Further, because our bodies make this therapeutic, there is no fear of it being rejected.”

Nair and her team found that human resistin decreases the number of pro-inflammatory cytokines -; small secreted proteins that aid cell-to-cell communication in immune responses -; by binding to “Toll-like receptor 4” (TLR4), its receptor. This binding blocks TLR4 signaling in immune and inflammatory cells.

TLR4, a molecule found on the surface of cells, is the innate receptor of our immune system and recognizes danger from foreign pathogens. During sepsis, for example, it recognizes lipopolysaccharide (LPS), the major component in the cell wall of the sepsis-causing bacteria. Too much LPS results in an overstimulation of TLR4, and the immune system goes into overdrive. Nair and her colleagues have found that when resistin binds to TLR4 it prevents TLR4 from recognizing LPS, eventually minimizing the immune response.

“Sepsis is a consequence of bacterial infection,” Nair said. “Patients can be treated with antibiotics to kill bacteria. But even if the bacteria are killed, LPS is left behind. As a result, the immune system goes into overdrive even with no infection still around. That’s when other means become necessary to kill the bacteria and calm the immune system down. If we can stop the excessive immune response, we can stop sepsis.”

William Harnett, a professor of molecular immunology at the University of Strathclyde in the United Kingdom, explained that in spite of representing a very common medical emergency, sepsis remains difficult to treat, with newly tested strategies proving disappointing.

“Using state-of-the-art experimental procedures, Meera Nair and colleagues now suggest a new approach, an intriguing development given this human resistin was previously considered to contribute to sepsis,” said Harnett, who was not involved in the research. “The novel data they present reveal how resistin, by interacting with TLR4, can block the inflammatory responses induced by bacterial products that lead to sepsis. This is certainly an exciting finding and a noteworthy development in the drive to find new treatments for sepsis.”

Nair’s team also worked with blood cells donated by healthy people and found that resistin bound to TLR4 even in these cells. In collaboration with clinicians at the Riverside University Health System Medical Center, the team will soon test blood cells from septic patients. The School of Medicine Dean’s Research Innovation Fund will support these preliminary sepsis studies focusing on clinical samples.

Nair noted that other labs have infected mice with worms to alleviate sepsis.

“Worms can infect an estimated two-billion people worldwide,” she said. “Worms have evolved with us for millions of years. They have adapted and can reside in us long term. To live inside us, they turn down our immune system. How do they accomplish this? It’s possible that resistin is involved.”

“It’s always been puzzling why worms living in the gut don’t cause more problems with sepsis, as they cause tissue damage in the gut and the gut is full of bacteria,” said P’ng Loke, an associate professor of microbiology at New York University, who was not involved in the research. “The results from Dr. Nair’s study identify resistin as an important molecule induced by worms that could help prevent sepsis.”

Nair is also excited about the prospects for a new therapeutic sepsis treatment developed in her lab. Called Retn N-pep, this new compound was made in collaboration with Maurizio Pellecchia, a professor of biomedical sciences at UCR, director of the Center for Molecular and Translational Medicine (MOLMED), and a co-author on the research paper.

“Retn N-pep blocked TLR4,” said Nair, who is a member of MOLMED. “It is smaller and more effective than human resistin in blocking inflammation in human blood cells. Potentially, it could inhibit any inflammatory disease involving TLR4. Dr. Pellecchia is now optimizing Retn N-pep to fold better and be more effective. Fortunately, all the chips fell into place at UCR to allow for this clinical collaboration, placing the university at the forefront of translational, therapeutic research.”

Pellecchia, who holds the Daniel Hays Endowed Chair in Cancer Research at UCR, said the project is the fruit of Nair’s ingenuity and perseverance.

“I am confident that Retn N-pep, based entirely on Dr. Nair’s pivotal discoveries, can be translated into an effective and innovative treatment for sepsis,” he said.

While the research from Nair’s lab focused only on sepsis, human resistin may be useful in modulating inflammation in TLR4-mediated diseases and treating conditions that involve overactive TLR4 activation, such as autoimmune diseases and inflammatory bowel disease.

Source:

Researchers Identify Hormone for Treating Sepsis

Tagged with:

About author

Related Articles