Stress Could Activate "Crosstalking" Cell Signals That Turn Body’s Natural Wound Healing Process Against It

Stress Could Activate “Crosstalking” Cell Signals That Turn Body’s Natural Wound Healing Process Against It:

Stress could activate “crosstalking” cell signals that decrease the body’s natural healing process after a wound occurs, according to a new study released today in STEM CELLS Translational Medicine. The finding helps explain how stress impairs healing and, conversely, could lead to a way to overcome chronic wounds resulting from serious burns and other skin injuries.
“Chronic wounds are a major global health problem, with annual costs in the United States alone of more than $23 billion,” said Roslyn Isseroff, M.D., of the University of California Davis and the Northern California Health Care System’s Department of Veterans Affairs. She was a lead investigator in the study along with Mohan R. Dasu, Ph.D.
“The precise process that prevents their healing is unclear except for two constants: a prolonged inflammatory response and the bacterial colonization of the wound bed. These two interrelated factors are thought to contribute to the wound’s chronic state.”
Previous studies had demonstrated an increase in epinephrine (adrenaline), as occurs during stress, produces an increase in the activity of TLR2 (Toll-like receptor 2), a protein that appears to stimulate the early inflammatory process needed to set the steps of healing in motion. Together they alter the ability of stem cells and keratinocytes, the barrier-forming cells that make up 90 percent of skin, to repair wound damage by slowing down the stem cells’ migration to the area and by promoting inflammation.
To compound the potential for damage, bacteria in the wound can activate the TLR2 system, and crosstalk to the epinephrine signaling system, creating a cycle of escalating damaging signals.
The Isseroff and Dasu team, which included colleagues at UC-Davis’s Institute for Regenerative Cures and California State University, decided to look at how increased epinephrine and TLR2 stimulation affected stem cells taken from bone marrow and keratinocytes by analyzing the “crosstalk” between their signaling pathways. The researchers tested their theory in cultured cells and in mice. In both instances they found that the crosstalk led to impaired healing, with elevated levels of TLR2 as well as MyD88 and IL-6, both of which regulate the activation of numerous pro-inflammatory genes, in the wounds.
“Thus, our data describe a recipe for decreasing cell migration and exacerbating inflammation via novel crosstalk between the adrenergic and Toll-like receptor pathways in wounds,” Dr. Dasu said.
“These findings have implications for understanding the mechanisms controlling the differing susceptibility to infections and immune/inflammatory-related conditions in wounds,” said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.
The full article, “Crosstalk Between Adrenergic and Toll-Like Receptors in Human Mesenchymal Stem Cells and Keratinocytes: A Recipe for Impaired Wound Healing,” can be accessed at
About STEM CELLS Translational Medicine: STEM CELLS TRANSLATIONAL MEDICINE (SCTM), published by AlphaMed Press, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.
About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes two other internationally renowned peer-reviewed journals: STEM CELLS® (, celebrating its 32nd year, is the world’s first journal devoted to this fast paced field of research. The Oncologist® (, also a monthly peer-reviewed publication, entering its 19th year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. All three journals are premier periodicals with global

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