Jeff L. Ellsworth

The proinflammatory cytokines IL-17A and IL-17F have a high degree of sequence similarity and share many biological properties. Both have been implicated as factors contributing to the progression of inflammatory and autoimmune diseases. Moreover, reagents that neutralize IL-17A significantly ameliorate disease severity in several mouse models of human disease. IL-17A mediates its effects through interaction with its cognate receptor, the IL-17 receptor (IL-17RA). We report here that the IL-17RA-related molecule, IL-17RC is the receptor for IL-17F. Notably, both IL-17A and IL-17F bind to IL-17RC with high affinity, leading us to suggest that a soluble form of this molecule may serve as an effective therapeutic antagonist of IL-17A and IL-17F. We generated a soluble form of IL-17RC and demonstrate that it effectively blocks binding of both IL-17A and IL-17F, and that it inhibits signaling in response to these cytokines. Collectively, our work indicates that IL-17RC functions as a receptor for both IL-17A and IL-17F and that a soluble version of this protein should be an effective antagonist of IL-17A and IL-17F mediated inflammatory diseases.

Using multiparameter flow cytometric analysis, we find that senescent cells accumulate in a unique cell-cycle compartment characterized in cell-cycle arrest in G1 and a significantly reduced nucleocytoplasmic ratio (genome size/cell mass) relative to cycling cells. With respect to gross cellular phenotype, the quiescent state of senescent cells differs from quiescence induced by density inhibition; the former is associated with a reduction in the nucleocytoplasmic ratio, while the latter is associated with an increase in the nucleocytoplasmic ratio. Senescent cells were present at all passages examined. The frequency of senescent cells was low in early-passage cultures and increased with passage number. Senescence of populations of IMR-90 cells reflects change in the relative frequency of these cells. The frequency of cells with karyotypic changes increased with the progressive accumulation of out-of-cycle cells.

BACKGROUND AND AIM: Recent epidemiological studies suggest that there is an inverse association between the frequent consumption of nuts and the risk of coronary heart disease (CHD), and clinical investigations suggest that diets high in nuts may reduce serum cholesterol levels. This study assessed whether the risk of death due to CHD and all causes is reduced in postmenopausal women who frequently consume nuts. METHODS AND RESULTS: In 1986, 34,111 postmenopausal women with no known cardiovascular disease reported the frequency of their consumption of nuts and other foods, as well as other CHD risk factors. During approximately 12 years of follow-up, 3726 women died, 657 from CHD. After adjustment for multiple risk factors for CHD and dietary variables, there was an inverse but not statistically significant association between frequent nut consumption (two or more 28.5 g servings per week compared with less than one serving per month) and death from CHD (relative risk 0.81; 95% confidence interval: 0.60-1.11). There was also a weak inverse association between frequent nut intake and all-cause mortality (relative risk 0.88; 95% confidence interval: 0.77-0.99, p for trend = 0.047). CONCLUSIONS: Frequent nut consumption may offer postmenopausal women modest protection against the risk of death from all causes and CHD.