TY - JOUR
T1 - TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes
AU - Yamasaki, Kenshi
AU - Kanada, Kimberly
AU - MacLeod, Daniel T.
AU - Borkowski, Andrew W.
AU - Morizane, Shin
AU - Nakatsuji, Teruaki
AU - Cogen, Anna L.
AU - Gallo, Richard L.
N1 - Funding Information:
We thank Anke Leichtle and Allen F Ryan for providing skin of Tlr2-/- mice, and Amy L Firth and Jason X Yuan for their assistance regarding measurements of intracellular calcium concentrations in keratinocytes. The NIH grants NIH R01-AR052728, NIH R01-AI052453, and a VA Merit Award to RLG, and grants from the National Rosacea Society (to KY and RLG) supported this work.
PY - 2011/3
Y1 - 2011/3
N2 - A diverse environment challenges skin to maintain temperature, hydration, and electrolyte balance while also maintaining normal immunological function. Rosacea is a common skin disease that manifests unique inflammatory responses to normal environmental stimuli. We hypothesized that abnormal function of innate immune pattern recognition could explain the enhanced sensitivity of patients with rosacea, and observed that the epidermis of patients with rosacea expressed higher amounts of Toll-like receptor 2 (TLR2) than normal patients. Increased expression of TLR2 was not seen in other inflammatory skin disorders such as atopic dermatitis or psoriasis. Overexpression of TLR2 on keratinocytes, treatment with TLR2 ligands, and analysis of TLR2-deficient mice resulted in a calcium-dependent release of kallikrein 5 from keratinocytes, a critical protease involved in the pathogenesis of rosacea. These observations show that abnormal TLR2 function may explain enhanced inflammatory responses to environmental stimuli and can act as a critical element in the pathogenesis of rosacea.
AB - A diverse environment challenges skin to maintain temperature, hydration, and electrolyte balance while also maintaining normal immunological function. Rosacea is a common skin disease that manifests unique inflammatory responses to normal environmental stimuli. We hypothesized that abnormal function of innate immune pattern recognition could explain the enhanced sensitivity of patients with rosacea, and observed that the epidermis of patients with rosacea expressed higher amounts of Toll-like receptor 2 (TLR2) than normal patients. Increased expression of TLR2 was not seen in other inflammatory skin disorders such as atopic dermatitis or psoriasis. Overexpression of TLR2 on keratinocytes, treatment with TLR2 ligands, and analysis of TLR2-deficient mice resulted in a calcium-dependent release of kallikrein 5 from keratinocytes, a critical protease involved in the pathogenesis of rosacea. These observations show that abnormal TLR2 function may explain enhanced inflammatory responses to environmental stimuli and can act as a critical element in the pathogenesis of rosacea.
UR - http://www.scopus.com/inward/record.url?scp=79951516747&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79951516747&partnerID=8YFLogxK
U2 - 10.1038/jid.2010.351
DO - 10.1038/jid.2010.351
M3 - Article
C2 - 21107351
AN - SCOPUS:79951516747
VL - 131
SP - 688
EP - 697
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 3
ER -