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ATP binding cassette transporter ABC1 is required for the release of interleukin‐1β by P2X 7 ‐stimulated and lipopolysaccharide‐primed mouse Schwann cells
Author(s) -
Marty Vincent,
Médina Chantal,
Combe Chantal,
Parnet Patricia,
Amédée Thierry
Publication year - 2005
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20138
Subject(s) - dids , microbiology and biotechnology , biology , transporter , receptor , atp binding cassette transporter , biochemistry , membrane , gene
Schwann cells are best known as myelinating glial cells of the peripheral nervous system, but they also participate actively in the sphere of immunity by producing pro‐inflammatory cytokines, such as interleukin‐1β (IL‐1β). In a previous study, we demonstrated that posttranslational processing of IL‐1β by immune‐challenged Schwann cells required the P2X 7 receptor. Remarkably, the release of IL‐1β was not associated with cell death, indicating the involvement of an active mechanism. ATP binding cassette (ABC) transporters are known to transport leaderless secretory proteins, such as IL‐1β; therefore, we investigated whether such transporters were at work in Schwann cells. Mouse Schwann cells expressed ABC1 transporter mRNA and displayed the functional protein. Glybenclamide and diisothiocyanato‐stilbene‐disulfonic acid (DIDS), two blockers of chloride fluxes that drive the export activity of ABC1 transporters, inhibited IL‐1β release without altering its intracellular processing. Enhancing chloride efflux potentiated the release of IL‐1β, while decreasing it led to a strong reduction in its release. Because the stimulation of the P2X 7 receptor also activates a chloride conductance, we investigated the possibility of a sole anionic pathway mobilized by the P2X 7 receptor and ABC1. Glybenclamide and DIDS had no significant effects on the P2X 7 ‐activated chloride current suggesting therefore the existence of two different pathways. In summary, ABC1 transporters are required for the release of IL‐1β by mouse Schwann cells. Being associated together with chloride conductance, P2X 7 receptors and ABC1 transporters delineate a subtle and complex regulation of IL‐1β production in mammalian Schwann cells. Furthermore, ABC1 transporters could be a target of therapeutic interest for regulating IL‐1β activity in neuroinflammation disorders. GLIA, 2004. © 2004 Wiley‐Liss, Inc.

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