title: Inflammatory mediators in autoimmune lacrimal gland disease in MRL/Mpj mice.
abstract: OBJECTIVE
  MRL/MpJ-fas(+)/fas(+) (MRL/+) and MRL/MpJ-fas(lpr)/fas(lpr) (MRL/lpr) mice are congenic substrains of mice that have spontaneously developing lacrimal and salivary gland inflammation and are models for the human disorder Sjögren's syndrome. Nitric oxide (NO) and tumor necrosis factor (TNF)-alpha are proinflammatory and potential mediators of tissue damage. The presence of the inducible form of nitric oxide synthase (iNOS), which catalyzes the production of NO, and the presence TNF-alpha in the lacrimal glands of MRL/MpJ mice were assessed.
  
  
  METHODS
  Lacrimal glands from MRL/+ and MRL/lpr mice, at ages 1 through 9 months, were evaluated by real-time RT-PCR for iNOS and TNF-alpha mRNA and by immunohistochemistry for the presence of iNOS and of TNF-alpha. Age-matched BALB/c lacrimal glands were used as the control.
  
  
  RESULTS
  By quantitative real-time PCR (qPCR), mRNA for iNOS was detected in the lacrimal glands in significantly greater amounts in both MRL/+ (median, normalized to 18S rRNA, 2.90; P < 0.0003) and MRL/lpr mice (median 6.84, P < 0.001) than in BALB/c mice (median 0.34). By qPCR, mRNA for TNF-alpha in the lacrimal glands was detected in significantly greater amounts in aged MRL/+ mice than in BALB/c mice (median, normalized to actin, 221.8 vs. 77.8, P = 0.011) and in MRL/lpr mice than in BALB/c mice (median 136.7 vs. 72.5, P = 0.001). Immunohistochemistry demonstrated both iNOS and TNF-alpha in scattered mononuclear cells throughout the lacrimal glands and in mononuclear cells at the junction of the focal inflammatory infiltrates and normal acinar tissue in both MRL/+ and MRL/lpr mice.
  
  
  CONCLUSIONS
  As demonstrated by the greater presence of iNOS and TNF-alpha in the lacrimal glands of MRL/MpJ mice than in control glands, both NO and TNF-alpha are potential mediators of lacrimal gland damage in these murine models of Sjögren's syndrome.
authors.affiliation: Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. djabs@jhmi.edu
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Jabs
authors.forename: Hérvé C
authors.initials: HC
authors.lastname: Gérard
authors.forename: Yuewang
authors.initials: Y
authors.lastname: Wei
authors.forename: Adam L
authors.initials: AL
authors.lastname: Campbell
authors.forename: Alan P
authors.initials: AP
authors.lastname: Hudson
authors.forename: Esen Karamursel
authors.initials: EK
authors.lastname: Akpek
authors.forename: Bella
authors.initials: B
authors.lastname: Lee
authors.forename: Robert A
authors.initials: RA
authors.lastname: Prendergast
authors.forename: Judith A
authors.initials: JA
authors.lastname: Whittum-Hudson
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D007124:Immunoenzyme Techniques; D018836:Inflammation Mediators / Q000378:metabolism*; D007765:Lacrimal Apparatus / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012859:Sjogren's Syndrome / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse