title: IL-15: a novel prosurvival signaling pathway in cardiomyocytes.
abstract: Cardiovascular disease is the leading cause of death in Western countries. A major limitation of current treatments is the inability to efficiently repair or replace dead myocardium. Recently, stem cell-based therapies have been explored as an avenue to circumvent current therapeutic limitations. Overall, these therapies seem to result in small improvements in the contractile function of the heart. The exact mechanism(s) of action that underlie these improvements remain unknown, and it is believed that paracrine effects play a significant role. Previously, we had reported that an extract derived from bone marrow cells, in the absence of any live cell, contained cardioprotective soluble factors. In this study, we identify IL-15 as a putative cardioprotectant within the bone marrow cells paracrine profile. Using an in vitro culture system, we assessed the ability of IL-15 to protect cardiomyocytes under hypoxic conditions. For the first time, we have identified IL-15 receptors on the surface of cardiomyocytes and delineated the signaling system by which hypoxic cardiomyocytes may be protected from cellular death and rescued from oxidative stress with IL-15 treatment.
authors.affiliation: *Department of Medicine, University of California, San Francisco, San Francisco, CA; †Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA; ‡Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA; and §San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA.
authors.forename: Yerem
authors.initials: Y
authors.lastname: Yeghiazarians
authors.forename: Norman
authors.initials: N
authors.lastname: Honbo
authors.forename: Isabella
authors.initials: I
authors.lastname: Imhof
authors.forename: Brandon
authors.initials: B
authors.lastname: Woods
authors.forename: Vanessa
authors.initials: V
authors.lastname: Aguilera
authors.forename: Jianqin
authors.initials: J
authors.lastname: Ye
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Boyle
authors.forename: Joel S
authors.initials: JS
authors.lastname: Karliner
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D019409:Interleukin-15 / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D053647:Receptors, Interleukin-15 / Q000187:drug effects / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D050796:STAT3 Transcription Factor