Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses.
One of the factors that contributes to the pathogenesis of acne is Propionibacterium acnes; yet, the molecular mechanism by which P. acnes induces inflammation is not known. Recent studies have demonstrated that microbial agents trigger cytokine responses via Toll-like receptors (TLRs). We investigated whether TLR2 mediates P. acnes-induced cytokine production in acne. Transfection of TLR2 into a nonresponsive cell line was sufficient for NF-kappa B activation in response to P. acnes. In addition, peritoneal macrophages from wild-type, TLR6 knockout, and TLR1 knockout mice, but not TLR2 knockout mice, produced IL-6 in response to P. acnes. P. acnes also induced activation of IL-12 p40 promoter activity via TLR2. Furthermore, P. acnes induced IL-12 and IL-8 protein production by primary human monocytes and this cytokine production was inhibited by anti-TLR2 blocking Ab. Finally, in acne lesions, TLR2 was expressed on the cell surface of macrophages surrounding pilosebaceous follicles. These data suggest that P. acnes triggers inflammatory cytokine responses in acne by activation of TLR2. As such, TLR2 may provide a novel target for treatment of this common skin disease.
Kim
Jenny
J
Division of Dermatology, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095, USA.
Ochoa
Maria-Teresa
MT
Krutzik
Stephan R
SR
Takeuchi
Osamu
O
Uematsu
Satoshi
S
Legaspi
Annaliza J
AJ
Brightbill
Hans D
HD
Holland
Diana
D
Cunliffe
William J
WJ
Akira
Shizuo
S
Sieling
Peter A
PA
Godowski
Paul J
PJ
Modlin
Robert L
RL
D000152:Acne Vulgaris / Q000209:etiology / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D029721:Drosophila Proteins; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D020382:Interleukin-18 / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011425:Propionibacterium acnes / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D016207:Cytokines; D029721:Drosophila Proteins; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D018664:Interleukin-12