Effects of gelsolin on macrophage inflammatory responses to orthopaedic implant wear debris.

The local effects of implant wear debris on surrounding tissue has been a major focus of many investigators. Although there have been improvements in implants, significant numbers of revision surgeries are performed to address these issues. Gelsolin (GSN) is a protein in the cytoplasm and circulating serum involved in actin breakdown as well as anti-inflammatory processes. In this study, we tested the hypothesis that GSN in the presence of wear debris in vitro decreases the inflammatory response of a human monocyte cell line. We utilized titanium-, polyethylene-, and cobalt-characterized wear particles in a 1:100 and a 1:500 cell-to-particle ratios in the presence of a low (0.2 µM) and normal (2.0 µM) concentrations of GSN and compared the inflammatory response to cells without GSN exposure. The results show that IL-6, IL-1, TNF-α, and PGE2 all increased with higher concentrations of GSN. Although the anti-inflammatory properties of GSN were not seen in this in vitro experiment, it has previously been shown that GSN does affect the inflammatory response of monocytes to orthopedic implant wear debris. The dose-response curve for GSN may have a bimodal profile, which should be further investigated.

Human epicardial adipokine messenger RNAs: comparisons of their expression in substernal, subcutaneous, and omental fat.

We compared the gene expression of inflammatory and other proteins by real-time quantitative polymerase chain reaction in epicardial, substernal (mediastinal) and subcutaneous sternal, upper abdominal, and leg fat from coronary bypass patients and omental (visceral) fat from extremely obese women undergoing bariatric surgery. We hypothesized that (1) epicardial fat would exhibit higher expression of inflammatory messenger RNAs (mRNAs) than substernal and subcutaneous fat and (2) epicardial mRNAs would be similar to those in omental fat. Epicardial fat was clearly different from substernal fat because there was a far higher expression of haptoglobin, prostaglandin D(2) synthase, nerve growth factor beta, the soluble vascular endothelial growth factor receptor (FLT1), and alpha1 glycoprotein but not of inflammatory adipokines such as monocyte chemoattractant protein-1, interleukin (IL)-8, IL-1beta, tumor necrosis factor alpha, serum amyloid A, plasminogen activator inhibitor-1, or adiponectin despite underlying coronary atherosclerosis. However, the latter inflammatory adipokines as well as most other mRNAs were overexpressed in epicardial fat as compared with the subcutaneous depots except for IL-8, fatty acid binding protein 4, the angiotensin II receptor 1, IL-6, and superoxide dismutase-2. Relative to omental fat, about one third of the genes were expressed at the same levels, whereas monocyte chemoattractant protein-1, cyclooxygenase-2, plasminogen activator inhibitor-1, IL-1beta, and IL-6 were expressed at far lower levels in epicardial fat. In conclusion, epicardial fat does not appear to be a potentially more important source of inflammatory adipokines than substernal mediastinal fat. Furthermore, the expression of inflammatory cytokines such as IL-6 and IL-1beta is actually higher in omental fat from obese women without coronary atherosclerosis. The data do not support the hypothesis that most of the inflammatory adipokines are expressed at high levels in epicardial fat of humans.

Resistin release by human adipose tissue explants in primary culture.

Resistin, also known as Fizz3 or ADSF, is a protein found in murine adipose tissue and inflammatory lung exudates. The present studies found that resistin was released by explants of human adipose tissue but the release was quite variable ranging from 3 to 158 ng/g over 48 h. The release of resistin was 250% greater by explants of omental than by explants of human subcutaneous abdominal adipose tissue. Resistin release by adipocytes was negligible as compared to that by the non-fat cells of adipose tissue. Leptin formation by adipocytes was 8-fold greater than its formation by the non-fat cells, while the formation of PAI-1 by adipocytes was 38% of that by the non-fat cells. The conversion of glucose to lactate as well as the formation of PGE(2) and IL-8 was approximately 15% of that by the non-fat cells. In contrast the release of IL-6 and IL-1beta by adipocytes was 4-7% of that by the non-fat cells while the formation of resistin and IL-10 by adipocytes was 2% of that by non-fat cells. The release of adiponectin by explants ranged from 1000 to 5000 ng/g over 48 h but did not correlate with that of resistin. The present data suggest that resistin release by explants of human adipose tissue in primary culture is largely derived from the non-fat cells present in the explants.