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
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 process...
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Published in | Glia Vol. 49; no. 4 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
01.01.2005
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Abstract | 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. |
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AbstractList | 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. |
Author | Parnet, Patricia Marty, Vincent Combe, Chantal Amedee, Thierry Medina, Chantal |
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