Nuclear Hormone Receptor Expression in Mouse Kidney and Renal Cell Lines

Nuclear hormone receptors (NHRs) are transcription factors that regulate carbohydrate and lipid metabolism, immune responses, and inflammation. Although several NHRs, including peroxisome proliferator-activated receptor-γ (PPARγ) and PPARα, demonstrate a renoprotective effect in the context of diabetic nephropathy (DN), the expression and role of other NHRs in the kidney are still unrecognized. To investigate potential roles of NHRs in the biology of the kidney, we used quantitative real-time polymerase chain reaction to profile the expression of all 49 members of the mouse NHR superfamily in mouse kidney tissue (C57BL/6 and db/m), and cell lines of mesangial (MES13), podocyte (MPC), proximal tubular epithelial (mProx24) and collecting duct (mIMCD3) origins in both normal and high-glucose conditions. In C57BL/6 mouse kidney cells, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and COUP-TFIII were highly expressed. During hyperglycemia, the expression of the NHR 4A subgroup including neuron-derived clone 77 (Nur77), nuclear receptor-related factor 1, and neuron-derived orphan receptor 1 significantly increased in diabetic C57BL/6 and db/db mice. In renal cell lines, PPARδ was highly expressed in mesangial and proximal tubular epithelial cells, while COUP-TFs were highly expressed in podocytes, proximal tubular epithelial cells, and collecting duct cells. High-glucose conditions increased the expression of Nur77 in mesangial and collecting duct cells, and liver x receptor α in podocytes. These data demonstrate NHR expression in mouse kidney cells and cultured renal cell lines and suggest potential therapeutic targets in the kidney for the treatment of DN

Serum amyloid A-induced IL-6 production by rheumatoid synoviocytes

AbstractIn this study, we investigated the role of serum amyloid A protein (SAA) in the production of interleukin-6 (IL-6) using rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). Recombinant SAA stimulation induced the production of pro-inflammatory cytokine, IL-6, from RA-FLS. The signaling events induced by SAA included the activation of the mitogen-activated protein kineases, p38 and JNK1/2 and the activation of nuclear factor-kappa B (NF-κB). Inhibitor studies have shown SAA-induced IL-6 production to be down-regulated by NF-κB inhibition and partially inhibited by p38 or JNK inhibitors. Our findings demonstrate that SAA is a significant inducer of IL-6, which is critically involved in RA pathogenesis

The role of IL-18 in the modulation of matrix metalloproteinases and migration of human natural killer (NK) cells

AbstractIn this study, we examined whether interleukin-18 (IL-18) affects natural killer (NK) cells' migration and matrix metalloproteinases (MMPs) production. We demonstrated that chemotaxis of human NK cells through basement membrane-like Matrigel was augmented by IL-18. As well, IL-18 stimulation induces the production of activated forms of matrix metalloproteinase-2 (MMP-2) as well as the production of pro-MMP-2 from NK cells. We also demonstrated that MT1-MMP expression on human NK cells, which is a major activator of MMP-2, was induced by IL-18 stimulation coordinated with MMP-2 activation. These data suggest that the MT1-MMP/MMP-2 system participates in the degradation of basement membrane components and thus contributes to NK cell migration