Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Deficiency of myeloid-related proteins 8 and 14 (Mrp8/Mrp14) does not block inflammaging but prevents steatosis

William R. Swindell _, Xianying Xing, Yi Fritz, Doina Diaconu, Daniel I. Simon, Nicole L. Ward and Johann E. Gudjonsson

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Oncotarget. 2016; 7:35535-35551. https://doi.org/10.18632/oncotarget.9550

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Abstract

William R. Swindell1,2, Xianying Xing2, Yi Fritz3, Doina Diaconu3, Daniel I. Simon4, Nicole L. Ward3,5,* and Johann E. Gudjonsson2,*

1 Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA

2 Department of Dermatology, University of Michigan, Ann Arbor, MI, USA

3 Department of Dermatology, Case Western Reserve University, Cleveland, OH, USA

4 Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA

5 The Murdough Family Center for Psoriasis, Case Western Reserve University, Cleveland, OH, USA

* These authors have contributed equally to this manuscript

Correspondence to:

William R. Swindell, email:

Keywords: B-cell; calgranulin; calprotectin; microarray; S100a8; Gerotarget

Received: March 19, 2016 Accepted: May 13, 2016 Published: May 21, 2016

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.


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