1. Bone marrow stem cell abnormality and diabetic complications
Kanna Nagaishi, Koji Ataka, Tomohisa Yamashita, Mineko Fujimiya Anat Rec (Hoboken) . 2012 Jun;295(6):917-21. doi: 10.1002/ar.22445.
Long-lasting diabetes impairs the function of multiple organs, which consists of degeneration of various tissues with increasing apoptosis of target cells. Recently, we found that hyperglycemia induced the appearance of abnormal cells in the bone marrow and cell fusion between bone marrow-derived cells and hepatocytes, peripheral neural cells, or renal tubular cells occurred in diabetic animals. Fused cells in these organs expressed TNFα, and accelerated apoptosis, suggesting that these events might be a cause of diabetic complications. In this review, we propose a new concept that bone marrow stem cell abnormality causes diabetic complications, and this concept might provide new strategies for treatment of diabetes-associated tissue damage.
2. Apolipoprotein M induces inhibition of inflammatory responses via the S1PR1 and DHCR24 pathways
Hong Liu, You-Pu Zhang, Xiao-Ying Zhang, Min Wang, Dong-Mei Di, Guang-Hua Luo, Xiang-Hong Zhan, Bin Wang, Ning Xu, Shuang Yao, Yang Yu Mol Med Rep . 2019 Feb;19(2):1272-1283. doi: 10.3892/mmr.2018.9747.
Apolipoprotein M (ApoM) is a type of apolipoprotein. It is well known that high‑density lipoprotein (HDL) decreases inflammatory responses via the apoM‑sphingosine‑1‑phosphate (S1P) pathway. The present study further investigated the importance of ApoM in the inhibitory effects of HDL on inflammation. Mice with an apoM gene deficiency (apoM‑/‑) were employed to investigate the effects of ApoM on the expression of interleukin‑1β (IL‑1β), monocyte chemotactic protein‑1 (MCP‑1), S1P receptor‑1 (S1PR1) and 3β‑hydroxysterol Δ‑24‑reductase (DHCR24), as compared with in wild‑type mice (apoM+/+). Furthermore, cell culture experiments were performed using a permanent human hybrid endothelial cell line (EA.hy926). Cells were cultured in the presence of recombinant human apoM (rec‑apoM) or were induced to overexpress apoM (apoMTg); subsequently, cells were treated with tumor necrosis factor‑α (TNF‑α), in order to investigate the effects of ApoM on IL‑1β and MCP‑1. The results demonstrated that the mRNA expression levels of IL‑1β and MCP‑1 were significantly higher in the liver following administration of lipopolysaccharide in apoM‑/‑ mice compared with in apoM+/+ mice. In cell culture experiments, when cells were pre‑cultured with rec‑apoM or were engineered to overexpress apoM (apoMTg), they exhibited decreased expression levels of IL‑1β and MCP‑1 following TNF‑α treatment compared with in normal apoM‑expressing cells (apoMTgN). Furthermore, the mRNA expression levels of IL‑1β and MCP‑1 were significantly elevated following addition of the S1PR1 inhibitor W146, but not by the scavenger receptor class B type I inhibitor, block lipid transport‑1 (BLT‑1), in apoMTg cells prior to TNF‑α treatment. Conversely, there were no differences in these inflammatory biomarkers under the same conditions in apoMTgN cells. The mRNA expression levels of DHCR24 were significantly reduced by the addition of BLT‑1 prior to TNF‑α treatment in apoMTg cells; however, there was no difference in the expression of this inflammatory biomarker in apoMTgN cells. In conclusion, ApoM displayed inhibitory effects against the inflammatory response in vivo and in vitro; these effects may be induced via the S1PR1 and DHCR24 pathways.
3. Regulation of macrophage function by human recombinant myeloperoxidase
N Moguilevsky, A Vaz, A Bollen, S S Lefkowitz, K C Mills, D L Lefkowitz Immunol Lett . 1993 Apr;36(1):43-9. doi: 10.1016/0165-2478(93)90067-c.
Myeloperoxidase is an enzyme which is found in the azurophilic granules of neutrophils and is associated with bactericidal, fungicidal, and tumoricidal activity. The present studies show that human recombinant myeloperoxidase (rec-MyPo) can regulate a number of macrophage (M phi) capacities and functions. Macrophages from mice exposed to rec-MyPo in vitro released reactive oxygen intermediates, tumor necrosis factor alpha (TNF alpha), and interferon alpha/beta (IFN alpha/beta). Enhanced target cell killing was also demonstrated with TNF alpha sensitive but not TNF alpha insensitive cells. Intravenous injection of rec-MyPo induced high titers of systemic TNF alpha and IFN alpha/beta. These results indicate that MyPo can function as an immunomodulator both in vitro and in vivo. Because of these actions, it is apparent that MyPo represents a previously unrecognized endogenous immunomodulator.
