A Functional Interplay between 5-Lipoxygenase andμ-Calpain Affects Survival and Cytokine Profile of Human Jurkat T Lymphocyte Exposed to Simulated Microgravity

Author:

Gasperi Valeria1,Rapino Cinzia23ORCID,Battista Natalia45ORCID,Bari Monica1,Mastrangelo Nicolina1,Angeletti Silvia6ORCID,Dainese Enrico45ORCID,Maccarrone Mauro56ORCID

Affiliation:

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

Abstract

A growing body of evidence strongly indicates that both simulated and authentic weightlessness exert a broad range of effects 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 flights. 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 ofµ-calpain. These events were paralleled by the unbalance of interleukin- (IL-) 2 and interferon- (INF-)γ, anti- and proapoptotic cytokines, respectively, that seemed to be dependent on the functional interplay between 5-LOX andµ-calpain. Indeed, we report unprecedented evidence that 5-LOX inhibition reduced apoptotic death, restored the initial IL-2/INF-γratio, and more importantly revertedµ-calpain activation induced by simulated microgravity.

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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