No abstract

CD40, a member of the TNF receptor family, has been characterized as an important T-B cell interaction molecule. In B cells it co-stimulates isotype switching, proliferation, adhesion and is involved in cell death regulation. In addition to B cells, CD40 expression was found on transformed cells and carcinomas. However, little is known about its functions in these cell types. Recent studies show that CD40 mediates the production of pro-inflammatory cyto-kines in non-hematopoietic cells, inhibits proliferation or induces cell death. In some cell types the apoptotic program triggered by CD40 is only executed when protein synthesis is blocked, suggesting the existence of constitutively expressed resistance proteins. Here we demonstrate that CD40, similar to the 55-kDa TNF receptor (p55TNFR), has a dual role in the regulation of apoptosis in such cells. In the fibroblast cell line SV80 both CD40 and the p55TNFR trigger apoptosis when protein synthesis is blocked with cycloheximide (CHX). Simultaneous activation of both receptors results in markedly enhanced cell death. However , CD40 activation more than 4 h prior to a challenge with TNF/CHX paradoxically conferred resistance to TNF-induced cell death. Protection correlated with NF-O B induction and up-regulation of the anti-apoptotic zinc finger protein A20. Overexpression of A20 in turn rendered SV80 cells resistant to TNF cytotoxicity. In conclusion, our data provide evidence that CD40 may regulate cell death in non-hematopoietic cells in a dual fashion: the decision upon apoptosis or survival of a CD40-activated cell seems to depend on its ability to up-regulate resistance factors.

No abstract

CD40, a member of the TNF receptor family, has been characterized as an important T-B cell interaction molecule. In B cells it co-stimulates isotype switching, proliferation, adhesion and is involved in cell death regulation. In addition to B cells, CD40 expression was found on transformed cells and carcinomas. However, little is known about its functions in these cell types. Recent studies show that CD40 mediates the production of pro-inflammatory cyto-kines in non-hematopoietic cells, inhibits proliferation or induces cell death. In some cell types the apoptotic program triggered by CD40 is only executed when protein synthesis is blocked, suggesting the existence of constitutively expressed resistance proteins. Here we demonstrate that CD40, similar to the 55-kDa TNF receptor (p55TNFR), has a dual role in the regulation of apoptosis in such cells. In the fibroblast cell line SV80 both CD40 and the p55TNFR trigger apoptosis when protein synthesis is blocked with cycloheximide (CHX). Simultaneous activation of both receptors results in markedly enhanced cell death. However , CD40 activation more than 4 h prior to a challenge with TNF/CHX paradoxically conferred resistance to TNF-induced cell death. Protection correlated with NF-O B induction and up-regulation of the anti-apoptotic zinc finger protein A20. Overexpression of A20 in turn rendered SV80 cells resistant to TNF cytotoxicity. In conclusion, our data provide evidence that CD40 may regulate cell death in non-hematopoietic cells in a dual fashion: the decision upon apoptosis or survival of a CD40-activated cell seems to depend on its ability to up-regulate resistance factors.

Background Return to sport testing is an established routine, especially for athletes who have ruptured their anterior cruciate ligament (ACL). Various tests are performed, often combined in test batteries, such as the Back-in-action (BIA) test battery. Unfortunately, pre-injury performance is often unknown, and only few athletes pass the high demands of these test batteries. Purpose The aim of the study was to determine the performance of under 18 American football players on the BIA to establish pre-injury sport specific benchmarks for future RTS testing and to compare these values to data from an age-matched reference group. Methods Fifty-three healthy male American football players underwent a functional assessment using the “Back-in-action” test battery evaluating agility, speed (Parkour-Jumps and Quick-Feet test), balance (using a PC based balance board), and power (Counter-Movement-Jump [CMJ]) as objective measures. Their results were compared with a previously tested reference group (RP) and within the american football players (AF) through three subgroups according to field playing position. Results Overall, the American football (AF) athletes showed lower balance scores for both legs (AF: 3.71/3.57/3.61; RP: 3.4/3.2/3.2; p<0.002) compared to the reference population (RP). CMJ height and Quick-Feet results were not statistically different (p>0.05), Parkour-Jump times (AF: 8.18/ 8.13 sec.; RP: 5.9/5.9sec.; p<0.001) were significantly slower. Power output in all CMJ’s (AF: 46.86/36.94/37.36 W/kg; RP: 43.2/29.5/29 W/kg; p<0.001) was significantly higher than the RP. Passing and running game involved players (G2 & G3) showed significantly better balance scores (G2+G3: 3.36/3.27/3.33; G1: 4.22/4.06/4.10; p<0.001), higher jump height (G2&G3: 38.87/24.02/24.96 cm; G1: 32.03/19.50/18.96 cm; p<0.001) and more watts/kg (G2&G3: 48.83/37.21/37.64 W/kg; G1: 43.95/36.88/36.53 W/kg; p<0.001) compared to blocking players like Linemen (G1) and to the age matched reference population (RP). Conclusion Only 53% of the healthy athletes would have been cleared for sport using the BIA test criteria, which highlights the challenging passing criteria. Despite significantly greater power measurements, scores of balance and agility were poorer compared to the reference group, especially for linemen. These data may serve as sport and position specific reference for high school American football players, instead of using the non-specific reference group data. Study design cross-sectional study- Level of evidence IIb