title: Antioxidant liposomes protect against CEES-induced lung injury by decreasing SAF-1/MAZ-mediated inflammation in the guinea pig lung.
abstract: We reported earlier in a guinea pig model that exposure of 2-chloroethyl ethyl sulfide (CEES), a mustard gas analog, causes lung injury associated with the activation of tumor necrosis factor alpha (TNF-alpha), mitogen activated protein kinases (MAPK) signaling, and activator protein-1 (AP-1) transcription factor. Our earlier studies also revealed that antioxidant liposomes can be used as antidotes. Proinflammatory cytokines IL-1, IL-6, and TNF-alpha, either alone or in combination, can induce the activation of another group of transcription factors, namely SAF-1 (serum accelerator factor-1)/MAZ (Myc-associated zinc finger protein). Phosphorylation of SAF-1 via MAPK markedly increases its DNA-binding and transactivational potential. The objective of the present study was to investigate whether CEES exposure causes activation of IL-1 beta, IL-6, and SAF-1/MAZ and whether these effects can be prevented by antioxidant liposomes. A single dose (200 microL) of the antioxidant liposome mixture was administered intratracheally after 5 min of exposure of CEES (0.5 mg/kg). The animals were sacrificed either 1 h or 30 days after CEES exposure. CEES exposure caused an upregulation of proinflammatory cytokines IL-6 and IL-1 beta in the lung along with an increase in the activation of transcription factor SAF-1/MAZ. The antioxidant liposomes treatment significantly blocked the CEES-induced activation of IL-6, IL-1 beta, and SAF-1/MAZ. This might suggest that antioxidant liposomes might offer a potential therapeutic strategy against inflammatory diseases associated with activation of these bioactive molecules.
authors.affiliation: Department of Cancer Biology, Meharry Medical College, Nashville, TN 37208, USA.
authors.forename: Sutapa
authors.initials: S
authors.lastname: Mukhopadhyay
authors.forename: Shyamali
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Bimal K
authors.initials: BK
authors.lastname: Ray
authors.forename: Alpana
authors.initials: A
authors.lastname: Ray
authors.forename: William L
authors.initials: WL
authors.lastname: Stone
authors.forename: Salil K
authors.initials: SK
authors.lastname: Das
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology*; D006168:Guinea Pigs; D007249:Inflammation / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008081:Liposomes / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009151:Mustard Gas / Q000031:analogs & derivatives* / Q000633:toxicity; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*
chemical_list: D000975:Antioxidants; D004268:DNA-Binding Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D008081:Liposomes; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein; C031278:2-chloroethyl ethyl sulfide; D009151:Mustard Gas