Induction of inflammatory reactions by lipopolysaccharide in hamster sebaceous glands and pilosebaceous units in vivo and in vitro

Abstract

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.

Augmentation of Gene Expression and Production of Promatrix Metalloproteinase 2 by Propionibacterium acnes-Derived Factors in Hamster Sebocytes and Dermal Fibroblasts: A Possible Mechanism for Acne Scarring

“…Together with our previous report that P. acnes facilitates the sebum production in the sebaceous glands, 20) it is suggested that P. acnes works cooperatively not only to facilitate sebum production but also to form acne scars due to the enhanced ECM degradation. These findings may provide novel insights into acne therapy in that compounds that inhibit MMP-2 production can be effective as anti-acne agents for the prevention and remission of scar formations.…”

“…So far, Choi et al 18) have also reported the augmentation of proMMP-2 production by P. acnes in human skin fibroblasts. In the present study, acne-CM and F-acnes, which exert the enhancement of sebaceous lipogenesis in hamsters in vivo and in vitro, 20) augmented the production of pro-MMP-2 in hamster sebocytes and dermal fibroblasts (Fig. 1).…”

“…10) Recently, we have reported that hamster sebocytes constitutively produce proMMP-2, which is immunologically similar to human proMMP-2. 20) In the present study, we demonstrated that hamster dermal fibroblasts as well as sebocytes constitutively and transcriptionally produced proMMP-2 (Figs. 1A, B, see untreated cells).…”

“…The cells were treated for 24 h with acne-CM (1ϫ10 6 and 1ϫ10 7 cells), F-acnes (1ϫ10 6 and 1ϫ 10 7 cells) or PGN (5-50 mg/ml) from Staphylococcus aureus (Sigma Chemical, St. Louis, MO, U.S.A.), in DMEM/ F12 or DMEM supplemented with 0.2% lactalbumin hydrolysate (Sigma). 20) In this series of experiments, hamster sebocytes and dermal fibroblasts were used as far as the 3rd and 6th passage levels, respectively.…”

“…20) The proteins separated on 12.5% acrylamide gel were electrotransferred onto nitrocellulose membrane. The membranes were reacted with sheep anti-(human proMMP-2) immunoglobulin G (IgG) (graciously provided by Prof. H. Nagase, the Kennedy Institute of Rheumatology, the Imperial College London, London, U.K.).…”