title: Deficiency of myeloid-related proteins 8 and 14 (Mrp8/Mrp14) does not block inflammaging but prevents steatosis.
abstract: The Mrp8 and Mrp14 proteins (calprotectin) accumulate within tissues during aging and may contribute to chronic inflammation. To address this possibility, we evaluated female calprotectin-deficient Mrp14-KO and wild-type (WT) mice at 5 and 24 months of age. However, there was no evidence that age-related inflammation is blunted in KO mice. Inflammation markers were in fact elevated in livers from old KO mice, and microarray analysis revealed more consistent elevation of genes specifically expressed by B-cells and T-cells. Adipose-specific genes, however, were less consistently elevated in aged KO mice, suggesting an anti-steatosis effect of Mrp8/14 deficiency. Consistent with this, genes decreased by the anti-steatosis agent SRT1720 were decreased in old KO compared to old WT mice. Expression of lipid metabolism genes was altered in KO mice at 5 months of age, along with genes associated with development, biosynthesis and immunity. These early-age effects of Mrp8/14 deficiency, in the absence of any external stressor, were unexpected. Taken together, our findings demonstrate a pro-steatosis rather than pro-inflammatory role of calprotectin within the aging liver. This appears to reflect a developmental-metabolic phenotype of Mrp14-KO mice that is manifest at a young age in the absence of pro-inflammatory stimuli.
authors.affiliation: Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA.|Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Swindell
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Xianying
authors.initials: X
authors.lastname: Xing
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fritz
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Doina
authors.initials: D
authors.lastname: Diaconu
authors.affiliation: Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Simon
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, OH, USA.|The Murdough Family Center for Psoriasis, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Ward
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Johann E
authors.initials: JE
authors.lastname: Gudjonsson
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D040501:Calgranulin A / Q000235:genetics*; D040502:Calgranulin B / Q000235:genetics*; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D007249:Inflammation / Q000235:genetics*; D039841:Leukocyte L1 Antigen Complex / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B; D006576:Heterocyclic Compounds, 4 or More Rings; D039841:Leukocyte L1 Antigen Complex; C576329:S100A9 protein, mouse; C086145:S100a8 protein, mouse; C525422:SRT1720
keywords: B-cell; Gerotarget; S100a8; calgranulin; calprotectin; microarray