Our data support the concept that inflammation, e.g. in psoriasis skin, may be maintained by the action of a positive feedback loop involving IL-1b and CCL20, which both have been shown to be produced by keratinocytes (24,26) as well as CCR6+ T cellderived IL-17. Of note, IL-17 was found to induce CCL20 (9,21) and IL-1b in keratinocytes. Both, IL-1b and IL-17 can induce each other and may lead to higher amounts of IL-1 family members, IL-17 and IL-22 in the tissue. In conclusion, our data suggest that IL-1b rather than IL-23 would be a promising upstream target to prevent the pro-inflammatory epidermal feedback response in psoriasis. Although there seems to exist a complex disturbance of the IL-1 family network in psoriasis (27), data from IL-1Ra knockout mice support the notion that unbalanced IL-1 activity contributes to the pathogenesis (28). It seems promising to address the underlying mechanisms in further investigations.
AcknowledgementsThis study was supported by DFG grant GRK 1441, DFG grant SFB 566, A6 and a joint project grant 2008 ⁄ R4 from The Royal Society. , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan, Tel.: +81-42-676-5717, Fax: +81-42-676-5734, e-mail: satotak@toyaku.ac.jp Abstract: Lipopolysaccharide (LPS) from Gram-negative bacteria has been reported to exert inflammatory reactions in epidermis, dermis, and sebaceous glands. Here, we demonstrated that the intradermal administration of Escherichia coli-derived LPS, three times a week for 4 weeks, to hamster auricle skin did not influence sebaceous morphology or sebum accumulation in sebaceous glands but in fact induced epidermal thickness. In addition, the administration of LPS, once a day for 2 days, augmented the production of cyclooxygenase 2 (COX-2) in sebaceous glands. Furthermore, LPS increased the production of prostaglandin F 2a (PGF 2a ) in hamster sebocytes. Moreover, the production of progelatinase A ⁄ promatrix metalloproteinase 2 (proMMP-2) was transcriptionally augmented by LPS and PGF 2a in hamster sebocytes. Therefore, these results suggest that LPS directly increases inflammation by augmenting COX-2, PGF 2a , and the PGF 2a -mediated proMMP-2 production in sebaceous glands as well as epidermal inflammatory events in skin disorders including acne and folliculitis.