title: Syk/Src pathway-targeted inhibition of skin inflammatory responses by carnosic acid.
abstract: Carnosic acid (CA) is a diterpene compound exhibiting antioxidative, anticancer, anti-angiogenic, anti-inflammatory, anti-metabolic disorder, and hepatoprotective and neuroprotective activities. In this study, the effect of CA on various skin inflammatory responses and its inhibitory mechanism were examined. CA strongly suppressed the production of IL-6, IL-8, and MCP-1 from keratinocyte HaCaT cells stimulated with sodium lauryl sulfate (SLS) and retinoic acid (RA). In addition, CA blocked the release of nitric oxide (NO), tumor necrosis factor (TNF)-α, and prostaglandin E₂ (PGE₂) from RAW264.7 cells activated by the toll-like receptor (TLR)-2 ligands, Gram-positive bacterium-derived peptidoglycan (PGN) and pam3CSK, and the TLR4 ligand, Gram-negative bacterium-derived lipopolysaccharide (LPS). CA arrested the growth of dermatitis-inducing Gram-positive and Gram-negative microorganisms such Propionibacterium acnes, Pseudomonas aeruginosa, and Staphylococcus aureus. CA also blocked the nuclear translocation of nuclear factor (NF)-κB and its upstream signaling including Syk/Src, phosphoinositide 3-kinase (PI3K), Akt, inhibitor of κBα (IκBα) kinase (IKK), and IκBα for NF-κB activation. Kinase assays revealed that Syk could be direct enzymatic target of CA in its anti-inflammatory action. Therefore, our data strongly suggest the potential of CA as an anti-inflammatory drug against skin inflammatory responses with Src/NF-κB inhibitory properties.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jueun
authors.initials: J
authors.lastname: Oh
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Choi
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yang
authors.forename: Heung Soo
authors.initials: HS
authors.lastname: Baek
authors.forename: Soon Ae
authors.initials: SA
authors.lastname: An
authors.forename: Lee Kyoung
authors.initials: LK
authors.lastname: Kwon
authors.forename: Jinsol
authors.initials: J
authors.lastname: Kim
authors.forename: Ho Sik
authors.initials: HS
authors.lastname: Rho
authors.forename: Song Seok
authors.initials: SS
authors.lastname: Shin
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
authors.forename: Sungyoul
authors.initials: S
authors.lastname: Hong
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008956:Models, Chemical; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012867:Skin / Q000201:enzymology*; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D000072377:Syk Kinase; D014212:Tretinoin / Q000494:pharmacology; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D045784:Abietanes; D000975:Antioxidants; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D010936:Plant Extracts; D012967:Sodium Dodecyl Sulfate; D014212:Tretinoin; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases; C018381:salvin