ATP binding cassette transporter ABC1 is required for the release of interleukin-1 beta by P2X sub(7)-stimulated and lipopolysaccharide-primed mouse Schwann cells

• Published in: Glia Vol. 49; no. 4
• Main Authors: Marty, Vincent, Medina, Chantal, Combe, Chantal, Parnet, Patricia, Amedee, Thierry
• Format: Journal Article
• Language: English
• Published: 01.01.2005
• ISSN: 0894-1491
• DOI: 10.1002/glia.20138

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-1 beta (IL-1 beta ). In a previous study, we demonstrated that posttranslational processing of IL- 1 beta by immune-challenged Schwann cells required the P2X sub(7) receptor. Remarkably, the release of IL-1 beta 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- 1 beta ; 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-1 beta release without altering its intracellular processing. Enhancing chloride efflux potentiated the release of IL-1 beta , while decreasing it led to a strong reduction in its release. Because the stimulation of the P2X sub(7) receptor also activates a chloride conductance, we investigated the possibility of a sole anionic pathway mobilized by the P2X sub(7) receptor and ABC1. Glybenclamide and DIDS had no significant effects on the P2X sub(7)-activated chloride current suggesting therefore the existence of two different pathways. In summary, ABC1 transporters are required for the release of IL-1 beta by mouse Schwann cells. Being associated together with chloride conductance, P2X sub(7) receptors and ABC1 transporters delineate a subtle and complex regulation of IL-1 beta production in mammalian Schwann cells. Furthermore, ABC1 transporters could be a target of therapeutic interest for regulating IL-1 beta activity in neuroinflammation disorders. GLIA, 2004.