Detrimental brain inflammation and the role of the interleukin 10 family members

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Burmeister, A. (2019). Detrimental brain inflammation and the role of the interleukin 10 family members. Unc Charlotte Electronic Theses And Dissertations.
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Abstract

Resident brain cells recognize pathogens and can initiate and/or regulate inflammation. Indeed, we have shown that stimulated glial cells rapidly produce inflammatory mediators, followed by the late production of anti-inflammatory cytokines such as IL-10. Here we have investigated the expression and function of other IL-10 family members in resident cells of the CNS, including IL-20 and IL-24. We have demonstrated that murine glial cells express IL-24 in a delayed manner in response to challenge with bacteria or their components. In addition, we have shown that glia constitutively express IL-20/24 receptors, and such expression is elevated in astrocytes following bacterial infection. Importantly, we have demonstrated that IL-24 inhibits the production of inflammatory cytokines by astrocytes and promotes the potentially neuroprotective functions of this cell type. In contrast, glial cells produce IL-20 constitutively and this cytokine acts on astrocytes increasing the expression of canonical inflammatory mediators and priming them for subsequent challenge. Additionally, we have begun to investigate the ability of substance P (SP) to augment the production of cytokines belonging to the IL-10 family. Here we report that non-human primate brain tissue and human glial cells constitutively express the SP receptor. We show that SP can augment the inflammatory and/or neurotoxic responses of human glial cells to disparate and clinically relevant bacterial pathogens. Interestingly, we have also demonstrated that SP can augment the production of the immunosuppressive cytokine, IL-19. Taken together, these data suggest that SP has the potential to affect the initiation and/or resolution of inflammation in human meningitis patients.

Details
Author

Burmeister, Amanda

Title

Detrimental brain inflammation and the role of the interleukin 10 family members

Physical Description

1 online resource (141 pages) : PDF

Date

2019

Degree Granting Institution

University of North Carolina at Charlotte

Abstract

Resident brain cells recognize pathogens and can initiate and/or regulate inflammation. Indeed, we have shown that stimulated glial cells rapidly produce inflammatory mediators, followed by the late production of anti-inflammatory cytokines such as IL-10. Here we have investigated the expression and function of other IL-10 family members in resident cells of the CNS, including IL-20 and IL-24. We have demonstrated that murine glial cells express IL-24 in a delayed manner in response to challenge with bacteria or their components. In addition, we have shown that glia constitutively express IL-20/24 receptors, and such expression is elevated in astrocytes following bacterial infection. Importantly, we have demonstrated that IL-24 inhibits the production of inflammatory cytokines by astrocytes and promotes the potentially neuroprotective functions of this cell type. In contrast, glial cells produce IL-20 constitutively and this cytokine acts on astrocytes increasing the expression of canonical inflammatory mediators and priming them for subsequent challenge. Additionally, we have begun to investigate the ability of substance P (SP) to augment the production of cytokines belonging to the IL-10 family. Here we report that non-human primate brain tissue and human glial cells constitutively express the SP receptor. We show that SP can augment the inflammatory and/or neurotoxic responses of human glial cells to disparate and clinically relevant bacterial pathogens. Interestingly, we have also demonstrated that SP can augment the production of the immunosuppressive cytokine, IL-19. Taken together, these data suggest that SP has the potential to affect the initiation and/or resolution of inflammation in human meningitis patients.

Genre

doctoral dissertations

Subjects--Topics

Biology

Degree

Ph.D.

Keywords

Cns
IL-20
IL-24
Inflammation
Interleukin

Subject Area

Biology

Advisor(s)

Marriott, Ian

Committee Members

Bost, Kenneth
Steck, Todd
Nelson, Daniel
Cho, Hansang

Degree Note

Thesis (Ph.D.)--University of North Carolina at Charlotte, 2019.

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Rights Holder Information

Copyright is held by the author unless otherwise indicated.

Identifier

Burmeister_uncc_0694D_11975

Permalink

http://hdl.handle.net/20.500.13093/etd:1213