Research Article A Functional Interplay between 5-Lipoxygenase and -Calpain Affects Survival and Cytokine Profile of Human Jurkat T Lymphocyte Exposed to Simulated Microgravity Valeria Gasperi, 1 Cinzia Rapino, 2,3 Natalia Battista, 4,5 Monica Bari, 1 Nicolina Mastrangelo, 1 Silvia Angeletti, 6 Enrico Dainese, 4,5 and Mauro Maccarrone 5,6 1 Department of Experimental Medicine & Surgery, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy 2 Faculty of Veterinary Medicine, University of Teramo, Piazza A. Moro 45, 64100 Teramo, Italy 3 StemTeCh Group, Via Colle dell’Ara, 66100 Chieti, Italy 4 Faculty of Bioscience, Technology for Food Agriculture and Environment, University of Teramo, Piazza A. Moro 45, 64100 Teramo, Italy 5 European Center for Brain Research (CERC), IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64-65, 00143 Rome, Italy 6 Center of Integrated Research, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy Correspondence should be addressed to Valeria Gasperi; valeria.gasperi@uniroma2.it, Enrico Dainese; edainese@unite.it, and Mauro Maccarrone; m.maccarrone@unicampus.it Received 15 May 2014; Accepted 18 August 2014; Published 16 September 2014 Academic Editor: Jack J. W. A. Van Loon Copyright © 2014 Valeria Gasperi et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A growing body of evidence strongly indicates that both simulated and authentic weightlessness exert a broad range of efects on mammalian tissues and cells, including impairment of immune cell function and increased apoptotic death. We previously reported that microgravity-dependent activation of 5-lipoxygenase (5-LOX) might play a central role in the initiation of apoptosis in human T lymphocytes, suggesting that the upregulation of this enzyme might be (at least in part) responsible for immunodepression observed in astronauts during space lights. Herein, we supplement novel information about the molecular mechanisms underlying microgravity-triggered apoptotic cell death and immune system deregulation, demonstrating that under simulated microgravity human Jurkat T cells increase the content of cytosolic DNA fragments and cytochrome c (typical hallmarks of apoptosis) and have an upregulated expression and activity of -calpain. hese events were paralleled by the unbalance of interleukin- (IL-) 2 and interferon- (INF-) , anti- and proapoptotic cytokines, respectively, that seemed to be dependent on the functional interplay between 5-LOX and -calpain. Indeed, we report unprecedented evidence that 5-LOX inhibition reduced apoptotic death, restored the initial IL-2/INF- ratio, and more importantly reverted -calpain activation induced by simulated microgravity. 1. Introduction Several studies have shown that authentic space condi- tions markedly alter physiological processes, thus leading to cardiovascular changes [1], loss of bone density [2, 3], muscle atrophy [2, 4], and immunodepression [5, 6]. To date, it is well established that cells of the immune system are severely afected by microgravity conditions [5–8]. In particular, alterations observed in astronauts and rodents lown in space included altered distribution and function of circulating leukocytes [9–11], lymphocytopenia [12–14], and impaired T cell activation [9, 14–16]. In addition, several in vivo and in vitro studies reported a weightlessness-dependent alteration of cytokine secretion from T-helper 1 (h1) and T- helper 2 (h2) cells that in turn results in a deregulation of cell-to-cell crosstalk as well as of inlammatory responses [9– 11, 17]. It has been reported that several proinlammatory h1 cytokines, including interferon- (INF-) , tumor necro- sis factor- (TNF-)  and interleukin- (IL-) 2, and anti- inlammatory h2 cytokines like IL-4 and IL-10, as well as leukaemia inhibitory factor (LIF), are related to programmed Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 782390, 10 pages http://dx.doi.org/10.1155/2014/782390