Researchers Discover Missing Links in Rosacea Inflammation

BARRINGTON, Illinois (August 10, 2017) — In a new study funded by the National Rosacea Society (NRS), medical scientists have connected the dots in the disease process of inflammation in rosacea, identifying a potential pathway for significant advances in the treatment of this widespread disorder affecting more than 16 million Americans.

In earlier research, the team led by Dr. Anna Di Nardo, associate professor of medicine of the University of California-San Diego, had determined that mast cells, located at the interface between the nervous system and vascular system, were a “missing link” between rosacea triggers and inflammation. They found that mast cells play a direct role in the activation of certain types of cathelicidins, an antimicrobial peptide involved in the innate immune response that is over-produced in people with rosacea.

Studying the process in mice, Dr. Di Nardo’s team determined that when exposed to a neuropeptide called PACAP, mast cells produce enzymes that trigger the production of cathelicidins. In mice bred to lack mast cells, however, this chain reaction did not occur.

Continuing their research, the scientists have now discovered that one of the proteins in cell membranes that facilitates communication between cells, known as transient receptor potential vanilloid 4 (TRPV4), plays a key role in activating mast cells in the skin of people with rosacea.1

In the new study, the researchers first examined whether cathelicidins were involved in spurring general TRPV production. After injecting cathelicidins into mice bred to exhibit human-like rosacea symptoms, two days later they saw significant increases in the expression of both TRPV2 and TRPV4. The researchers then tested the findings in the laboratory (in vitro) in both mouse and human mast cell cultures, confirming that cathelicidin increases the expression of TRPV4 and also determining that TRPV4 regulates the inflammation caused by mast cells.

Dr. Di Nardo's team further identified a protein receptor on mast cells known as MRGX2 as the likely pathway to TRPV4 activation by cathelicidins. By turning off MRGX2 in mast cells, they were able to prevent TRPV4 from reacting to cathelicidins, which in turn prevented the mast cells from triggering an inflammatory immune response associated with rosacea.

“Although more work needs to be done, these findings suggest that potential therapies may be developed specifically to block TRPV4 as a direct means of treating or preventing inflammation in patients with rosacea,” Dr. Di Nardo said. “We are grateful to the many rosacea patients whose donations to the NRS research grants program have made this effort possible.

What Is Rosacea?

Rosacea is a chronic disorder of the facial skin that typically first strikes anytime after age 30, and may initially resemble a simple sunburn or an inexplicable blush. Suddenly, without warning, a flush comes to their cheeks, nose, chin or forehead. Then just when they start to feel concerned, the redness disappears.

Unfortunately, it happens again and again, becoming ruddier and lasting longer each time, and eventually visible blood vessels may appear. Without treatment, bumps and pimples often develop, growing more extensive over time, and burning, itching and stinging are common.

In severe cases, especially in men, the nose may become enlarged from the development of excess tissue. This is the condition that gave comedian W.C. Fields his trademark red, bulbous nose. In some people the eyes are also affected, feeling irritated and appearing watery or bloodshot. Severe cases of this condition, known as ocular rosacea, can result in reduced visual acuity.

About the Research Grants Program

Perhaps nowhere else in dermatology is so little known about a disorder that affects so many. Because the cause of rosacea is unknown and there is no cure, the National Rosacea Society’s research grants program was established in 2000 to encourage and support research into the potential causes and other key aspects of this condition that may lead to improvements in its treatment and potential prevention or cure.

Entirely supported by donations from rosacea patients, the NRS research grants program has awarded more than $1.5 million to support a wide range of rosacea-related studies. Grants for 66 studies have been awarded to date, and have led to further investigations in such promising areas as the pathogenesis, progression, mechanism of action, cell biology and genetic factors of this widespread disorder. More information about the research grants program may be found online at

About the National Rosacea Society

The National Rosacea Society is the world’s largest organization dedicated to improving the lives of the estimated 16 million Americans who suffer from this widespread but poorly understood disorder. Its mission is to raise awareness of rosacea, provide public health information on the disorder and support medical research that may lead to improvements in its management, prevention and potential cure.

Comprehensive information and materials on rosacea are available on the NRS website at The NRS may also be followed on Facebook, Twitter and Pinterest for up-to-date information and tips on rosacea. Further information may be obtained by writing the National Rosacea Society, 111 Lions Dr., Ste. 216, Barrington, Illinois 60010; via email at; or by calling its toll-free number at 1-888-NO-BLUSH.



1. Mascarenhas NL, Wang Z, Chang YL, Di Nardo A. TRPV4 mediates mast cell activation in cathelicidin-induced rosacea inflammation. J Invest Dermatol 2017;137:972-5.

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