Pro-inflammatory effects of DEHP in SGBS-derived adipocytes and THP-1 macrophages.

In the member countries of the Organization for Economic Co-operation and Development (OECD), overweight and obesity affect the majority of the population. The use of environmental chemicals, such as the plasticizer DEHP, has largely increased simultaneously with this development. DEHP is an "obesogen" that interferes with normal adipocyte differentiation and energy homeostasis. Obesity in turn is accompanied by chronic low-grade adipose tissue inflammation, leading to metabolic disorders such as type II diabetes. The main actors in adipose tissue inflammation are adipocytes and macrophages. However, the impact of DEHP on adipose tissue inflammation and the crosstalk between adipocytes and macrophages are unknown and the subjects of the current study. The influence of DEHP on inflammation was investigated in human Simpson-Golabi-Behmel syndrome (SGBS)-derived adipocytes and human THP-1 macrophages. The proinflammatory markers IL8, MCP1, IL1ß, TNFα and others were measured (qRT-PCR, ELISA) in SGBS-derived adipocytes treated with DEHP [day 0 (d0)-d4; 50 µg/ml] and THP-1 macrophages cultured with conditioned medium (CM) from DEHP-treated adipocytes (SGBS-CM) (from d4 and d8). DEHP exposure led to a proinflammatory state in SGBS-derived adipocytes (e.g., increased secretion of IL8 and MCP1). Surprisingly, exposure of THP-1 macrophages to SGBS-CM did not show DEHP-induced effects. However, we demonstrated that medium containing (pre)adipocyte-secreted factors had a significant impact on the expression and secretion of macrophage and inflammatory markers in THP-1 macrophages in general and led to the significantly increased accumulation of intracellular lipid droplets.

Chromosomal aberrations are shared by malignant plasma cells and a small fraction of circulating CD19+ cells in patients with myeloma and monoclonal gammopathy of undetermined significance.

In the present study, we aimed to identify distinct structural and numerical chromosomal aberrations in peripheral blood B cells of patients with myeloma and monoclonal gammopathy of undetermined significance (MGUS), which reflect changes thought to occur at different stages of the disease process. Peripheral blood from 12 patients with multiple myeloma and three patients with MGUS was investigated for the occurrence of retinoblastoma-1 gene deletions, p53 gene deletions and numerical aberrations demonstrated previously to be present in the patients' bone marrow CD138+ cells. By combining immunocytochemical staining for light chains and interphase fluorescence in situ hybridization (FISH), aberrant light-chain +ve cells were detected in the circulating CD19+ cell fraction. Each kind of chromosomal change present in the myeloma tumour cells was found to be shared by a small fraction of CD19+ cells (0.1-1.8%; median 0.36%, n = 6). In one MGUS patient, aberrant cells could be identified with a frequency of 0.34% within the CD19-sorted cell fraction. Clonotypic cells were detected with a frequency of 0.01-0.07% of peripheral blood nucleated cells by m-RNA in situ hybridization with patient-specific probes in three investigated patients. These results provide evidence that the circulating clonotypic B cells are closely related to the malignant plasma cells in myeloma and MGUS.