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Published on: July 26, 2017
Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses
Jenny Kim1, Maria-Teresa Ochoa, Stephan R Krutzik
1Division of Dermatology, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095, USA.
Abstract:
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.
Insights
Propionibacterium acnes triggers inflammation in acne by activating Toll-like receptor 2 (TLR2). This discovery suggests TLR2 as a potential therapeutic target for acne treatment.
Area of Science:
- Dermatology
- Immunology
- Microbiology
Background:
- Propionibacterium acnes (P. acnes) contributes to acne pathogenesis.
- The molecular mechanisms of P. acnes-induced inflammation remain unclear.
- Microbial agents can trigger cytokine responses through Toll-like receptors (TLRs).
Purpose of the Study:
- To investigate if Toll-like receptor 2 (TLR2) mediates P. acnes-induced cytokine production in acne.
- To explore the role of TLR2 in the inflammatory pathways of acne.
Main Methods:
- Transfection of TLR2 into a nonresponsive cell line to assess NF-kappa B activation.
- Utilizing peritoneal macrophages from wild-type and knockout mice (TLR6, TLR1, TLR2).
- Analyzing IL-12 p40 promoter activity and cytokine (IL-12, IL-8) protein production in human monocytes.
- Examining TLR2 expression in acne lesions using immunohistochemistry.
Main Results:
- P. acnes induced NF-kappa B activation in cells transfected with TLR2.
- Macrophages from TLR2 knockout mice did not produce IL-6 in response to P. acnes.
- P. acnes activated IL-12 p40 promoter activity via TLR2.
- P. acnes stimulated IL-12 and IL-8 production in human monocytes, inhibited by anti-TLR2 antibodies.
- TLR2 was found on macrophages within acne lesions.
Conclusions:
- P. acnes activates inflammatory cytokine responses in acne through TLR2.
- TLR2 plays a significant role in mediating the inflammatory process of acne.
- TLR2 represents a potential novel therapeutic target for acne treatment.
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