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dc.contributor.advisorLangeland, James A., 1964-
dc.contributor.advisorFranz, Briana L.
dc.contributor.authorDavidson, Matthew D.
dc.descriptioniv, 32 p.en_US
dc.description.abstractInflammation is a protective response to pathogens, but can have dangerous immunopathological consequences including shock. One mediator of inflammation is Toll-like receptor 4 (TLR4), which binds Pathogen-Associated-Molecular-Patterns and endogenous ligands related to host damage and repair. TLR4 agonism activates the transcription factor NF-κB, which induces genes encoding proinflammatory cytokines, such as interleukin 8 (IL-8). IL-8 attracts neutrophils and regulates their migration. Lipopolysaccharide (LPS) is a constituent of the outer cell wall of Gram negative bacteria and a potent TLR4 agonist. TLR4 is the sole mediator of the inflammatory response to LPS, making LPS a useful positive control. We investigated inhibition of the LPSinduced, TLR4-mediated, inflammatory response by naloxone in the human monocyte cell line THP-1. THP-1 cells demonstrated dose-dependent IL-8 secretion (32.3 – 1841.8 pg/mL) in response to the known TLR4 agonist LPS. Naloxone alone did not elicit IL-8 secretion (2.94 – 3.59 pg/mL) and showed no interference with IL-8 detection by ELISA. Co-administration of LPS and naloxone greatly reduced LPS-induced-IL-8 secretion. These data provide evidence of a functioning TLR4/NF-κB pathway in THP-1 cells. These data also suggest inhibition of this pathway in THP-1 cells by naloxone in the presence of a known agonist, however, the point of interference remains undetermined. These findings have significant implications for immunological research in THP-1 cells and for the administration of naloxone in immunocompromised individuals.en_US
dc.description.sponsorshipCeeTox Inc. Kalamazoo, Michigan.
dc.publisherKalamazoo Collegeen_US
dc.relation.ispartofKalamazoo College Biology Senior Individualized Projects Collection
dc.rightsU.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.
dc.titleNaloxone, an Opioid Antagonist, Inhibits Inflammatory Toll-like Receptor 4 Signalingen_US
KCollege.Access.ContactIf you are not a current Kalamazoo College student, faculty, or staff member, email to request access to this thesis.

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  • Biology Senior Individualized Projects [1489]
    This collection includes Senior Individualized Projects (SIP's) completed in the Biology Department. Abstracts are generally available to the public, but PDF files are available only to current Kalamazoo College students, faculty, and staff.

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