Apoptosis and inflammatory response in human astrocytes are induced by a transmissible cytotoxic agent of neurological origin.
We demonstrated the presence of an in vitro transmissible cytotoxic agent (TCA) in the cerebrospinal fluid (CSF) of patients with different acute neurological diseases. The nature of this agent is still a matter of study since repeated attempts have failed to identify it as a conventional infectious agent. Here, we describe the mechanisms through which TCA affects human astrocytes, demonstrating: a late apoptotic process, mediated by caspases 9 and 3 activation, involving the Bcl2-Bak-axis; an early and late p38 MAPK activation; an interference with the IL-8 and MCP-1 secretory response. These in vitro data provide initial evidence of TCA involvement as a pro-apoptotic and pro-inflammatory signal, directly affecting astrocytic behavior. The implications of these findings in certain neurological diseases will be discussed.
Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Francesca
F
Beretti
Department of Diagnostic, Clinic and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
Andrea
A
Ardizzoni
Department of Diagnostic, Clinic and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
Claudio
C
Cermelli
EURAC research, Center for Biomedicine, via Galvani 31, 39100, Bolzano, Italy.
Marianna
M
Guida
Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Tullia
T
Maraldi
Department of Laboratories, Pathological Anatomy and Legal Medicine, University of Modena and Reggio Emilia, Italy.
Paola
P
Pietrosemoli
Department of Diagnostic, Clinic and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
Simona
S
Paulone
Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Anto
A
De Pol
Department of Diagnostic, Clinic and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
Elisabetta
E
Blasi
Department of Laboratories, Pathological Anatomy and Legal Medicine, University of Modena and Reggio Emilia, Italy.
Marinella
M
Portolani
D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D003603:Cytotoxins / Q000378:metabolism / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*
D003603:Cytotoxins
Apoptosis; Chemokines/cytokines; Cytotoxic factor; Misfolded proteins