TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes.
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.
Division of Dermatology, Department of Medicine, University of California, San Diego, VA San Diego Health Care System, San Diego, California, USA. kyamasaki@med.tohoku.ac.jp
Kenshi
K
Yamasaki
Kimberly
K
Kanada
Daniel T
DT
Macleod
Andrew W
AW
Borkowski
Shin
S
Morizane
Teruaki
T
Nakatsuji
Anna L
AL
Cogen
Richard L
RL
Gallo
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D001706:Biopsy; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011425:Propionibacterium acnes / Q000302:isolation & purification / Q000502:physiology; D012393:Rosacea / Q000378:metabolism* / Q000473:pathology; D057057:Serine Proteases / Q000378:metabolism*; D012867:Skin / Q000382:microbiology / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D057057:Serine Proteases; C400147:KLK5 protein, human; D007610:Kallikreins; D002118:Calcium; D054804:Cathelicidins