title: Novel anti-acne actions of nadifloxacin and clindamycin that inhibit the production of sebum, prostaglandin E(2)  and promatrix metalloproteinase-2 in hamster sebocytes.
abstract: Acne vulgaris is characteristic of excess sebum production and the induction of inflammatory reactions, for example, the augmentation of cytokine, prostaglandin (PG) and matrix metalloproteinase (MMP) production in sebaceous glands and pilosebaceous units. As Propionibacterium acnes is considered to be involved in the aggravation of acne vulgaris, antimicrobial agents have been found to be effective for treating acne leading to the remission of inflammation. However, it is not fully understood whether antimicrobial agents influence sebum production and/or the inflammatory reactions in sebaceous gland cells (sebocytes). In the present study, topical antimicrobial agents such as nadifloxacin (NDFX) and clindamycin (CLDM) decreased the production of triacylglycerols (TG), which are a major component of sebum in insulin-differentiated hamster sebocytes. These antibiotics also suppressed insulin-augmented gene expression and the production of perilipin, by which intracellular lipid droplet formation was concomitantly inhibited. On the other hand, peptidoglycan (PGN) from Gram-positive bacteria dose-dependently increased TG production in hamster sebocytes. The augmented TG production was decreased by treating NDFX or CLDM. Furthermore, NDFX and CLDM inhibited the PGN-augmented PGE(2)  production in the sebocytes. Moreover, NDFX, but not CLDM, suppressed the PGN-augmented gene expression and production of pro-MMP-2/progelatinase A in hamster sebocytes. Therefore, these results provide novel evidence that NDFX and CLDM exhibit anti-lipogenesis and anti-inflammatory activities against insulin- or PGN-activated sebocytes which at least partly mimic acne pathology in vitro. Moreover, NDFX for acne therapy is likely to be effective in not only inhibiting microbial proliferation but also in preventing the onset of acne scar formation.
authors.affiliation: Departments of Biochemistry and Molecular Biology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. satotak@toyaku.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Shirane
authors.forename: Norihisa
authors.initials: N
authors.lastname: Noguchi
authors.forename: Masanori
authors.initials: M
authors.lastname: Sasatsu
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D002981:Clindamycin / Q000494:pharmacology*; D006224:Cricetinae; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000235:genetics; D024841:Fluoroquinolones / Q000494:pharmacology*; D018093:Gelatinases / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D010457:Peptidoglycan / Q000494:pharmacology; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics; D011807:Quinolizines / Q000494:pharmacology*; D012627:Sebaceous Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012629:Sebum / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002352:Carrier Proteins; D004792:Enzyme Precursors; D024841:Fluoroquinolones; D010457:Peptidoglycan; D000070778:Perilipin-1; D010750:Phosphoproteins; D011807:Quinolizines; D002981:Clindamycin; C062127:nadifloxacin; D051048:Diacylglycerol O-Acyltransferase; D018093:Gelatinases; C069860:progelatinase; D015232:Dinoprostone