Scientists make new discoveries on role of signaling molecule in RDEB
Study IDs molecular feedback loop that may drive inflammation in rare disease
An inflammatory signaling molecule called interleukin-6 (IL-6) is produced at high levels in skin wounds of people with recessive dystrophic epidermolysis bullosa (RDEB), a new study reports.
Its findings indicate that a molecular feedback loop involving another protein called serum amyloid A (SAA) drives excessive production of IL-6 in skin cells.
“Our observations might help uncover the molecular mechanisms for the induction of IL-6-related systemic [body-wide] complications,” the investigators wrote.
The study, “Elevated expression of interleukin-6 (IL-6) and serum amyloid A (SAA) in the skin and the serum of recessive dystrophic epidermolysis bullosa: Skin as a possible source of IL-6 through Toll-like receptor ligands and SAA,” was published in Experimental Dermatology.
Scientists study levels of inflammatory signaling molecule IL-6
RDEB is a type of dystrophic epidermolysis bullosa, which itself is a type of EB, and is marked by fragile skin that blisters easily. People who have any form of the genetic skin disorder also often experience other related health problems, ranging from anemia to certain forms of cancer.
One of the main reasons these issues may develop in people with RDEB is because patients’ bodies are typically in a state of long-term, chronic inflammation.
The world is full of bacteria and other infectious organisms that can cause problems inside the body. In most people, the skin itself is a critical barrier for keeping these pathogens, or disease-causing agents, out of the body. But for people with RDEB, blisters and wounds make it easier for microscopic invaders to get into the body, and the body responds by launching an inflammatory counterattack.
IL-6 is a signaling molecule that drives inflammation, and studies have suggested that IL-6 levels are increased in RDEB. One recent study found that RDEB patients with more extensive wounds tend also to have higher IL-6 levels.
To learn more, scientists in Japan now measured IL-6 levels in the blood of seven patients with RDEB. Their findings showed these RDEB patients had higher IL-6 levels than were seen in people with other skin disorders.
“We observed markedly elevated serum [blood] levels of IL-6 in RDEB patients compared to patients with other chronic inflammatory disorders, such as atopic dermatitis or psoriasis,” the researchers wrote.
High levels of IL-6 found in skin cells of RDEB patients’ wounds
The scientists also analyzed skin samples from the RDEB patients’ wounds, and found that skin cells in the wounds expressed high levels of IL-6. This supports the idea that the skin is a main source of IL-6 in RDEB.
High levels of the protein SAA also were found in blood and skin samples from RDEB patients, according to the researchers.
SAA is known to be produced by the activation of toll-like receptors — immune proteins that function as detectors for invading bacteria.
In a battery of further experiments in skin cells, the researchers showed that activating toll-like receptors led to increased production of both SAA and IL-6. The team further showed that SAA itself also could activate toll-like receptors, which triggered the production of more IL-6 and more SAA, which further activates toll-like receptors, and so forth.
Based on these findings, the researchers concluded that “the persistent expression of IL-6 and SAA in RDEB patients could be linked to continuous production of SAA” that leads to an “inflammatory feedback loop” in patients’ skin cells.
More research is needed, but the team noted that their findings “might help to find [a potential treatment] candidate to modulate inflammatory conditions of RDEB.”
One notable limitation of these cell studies, according to the researchers, is that they were done using cell lines, not cells from RDEB patients. Thus, further work is needed to confirm whether these findings are applicable in people with the disease.
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