title: Isorhamnetin Attenuates Staphylococcus aureus-Induced Lung Cell Injury by Inhibiting Alpha-Hemolysin Expression.
abstract: Staphylococcus aureus, like other gram-positive pathogens, has evolved a large repertoire of virulence factors as a powerful weapon to subvert the host immune system, among which alpha-hemolysin (Hla), a secreted pore-forming cytotoxin, plays a preeminent role. We observed a concentration-dependent reduction in Hla production by S. aureus in the presence of sub-inhibitory concentrations of isorhamnetin, a flavonoid from the fruits of Hippophae rhamnoides L., which has little antibacterial activity. We further evaluate the effect of isorhamnetin on the transcription of the Hla-encoding gene hla and RNAIII, an effector molecule in the agr system. Isorhamnetin significantly down-regulated RNAIII expression and subsequently inhibited hla transcription. In a co-culture of S. aureus and lung cells, topical isorhamnetin treatment protected against S. aureus-induced cell injury. Isorhamnetin may represent a leading compound for the development of anti-virulence drugs against S. aureus infections.
authors.affiliation: Department of Dermatology, Second Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun 130041, P.R. China.
authors.forename: Lanxiang
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Dermatology, Second Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun 130041, P.R. China.
authors.forename: Hongen
authors.initials: H
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130021, P.R. China.
authors.forename: Laiying
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Second Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun 130041, P.R. China.
authors.forename: Zexin
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Dermatology, Second Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun 130041, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Dermatology, Second Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun 130041, P.R. China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Dermatology, Second Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun 130041, P.R. China.
authors.forename: Xuming
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Dermatology, Second Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun 130041, P.R. China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wang
mesh_terms: D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism / Q000633:toxicity; D015536:Down-Regulation / Q000187:drug effects; D006460:Hemolysin Proteins / Q000235:genetics* / Q000378:metabolism / Q000633:toxicity; D031281:Hippophae / Q000737:chemistry*; D006801:Humans; D008168:Lung / Q000276:immunology / Q000382:microbiology; D055370:Lung Injury / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D010936:Plant Extracts / Q000494:pharmacology*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D010936:Plant Extracts; C021091:staphylococcal alpha-toxin; C047368:3-methylquercetin; D011794:Quercetin
keywords: Staphylococcus aureus; alpha-hemolysin; anti-virulence; isorhamnetin