SATURDAY

October 16

SESSION 4

4:00– 4:15

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TOPICAL RETINOIDS AND THEIR EFFECT ON INFLAMMATORY MEDIATORS IN ACNE

Sewon Kang

In a seminal paper published in “Infection and Immunity” in 1995, Dr. James Leyden's group demonstrated the presence of a soluble factor of Proprionibacterium acnes ( P. acnes ) that induced proinflammatory cytokine production in human monocytic cell lines. Although distinct from lipopolysaccharide (LPS), this soluble factor is LPS-like in that its activity was dependent on the presence of CD14, a so-called pattern recognition receptor for LPS and other lipid containing ligands. Observed induction of TNF a and IL-1 b in the cell lines by P. acnes product was most likely occurring through, at the time unrecognized, toll-like receptor (TLR) activation. A mammalian homologue of a drosophila protein known as toll, TLR is emerging as key regulator of host responses to infection. This transmembrane protein has a cytoplasmic portion that is homologous to the IL-1 receptor and hence could trigger signaling cascade that activates NF- k B. The inflammatory cytokines produced, working via an autocrine and paracrine mechanisms through their respective receptors, can now amplify the signaling pathways that activate the AP-1 transcription factor. AP-1 regulated matrix metalloproteinases (MMPs) will degrade and repair dermal matrix, which will lead to acne scarring. Data from human in vivo studies support this model of acne inflammation and matrix alteration. Based on this model, TLR , NF - k B, AP-1, and MMPs are all rational targets to aim for in the treatment of acne. Furthermore, the model indicates that drugs like retinoids improve acne, not only through their ability to normalize perifollicular differentiation of keratinocytes, but also as an anti-AP-1 mechanism.

Click here to return to Dermatology Update 2004 Schedule and Abstracts