MAP Kinase Inhibition Prevents Induction of IL-6 and TNFα by Porin B of Neisseria meningitidis in Murine Macrophages
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Authors
Jorth, Peter Allan
Issue Date
2006
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
This study examined the signaling events that follow the stimulation of the
immune system by Neisseria meningitidis Porin B (PorB). This bacterial molecular
component is known to induce an immune response via Toll-like receptor 2 (TLR2);
however, the specific details of the signaling pathway have yet to be determined. Murine
bone marrow-derived macrophages (BMDMs) in cell culture were pretreated with
specific mitogen-activated protein kinase (MAPK) inhibitors and then stimulated with
PorB, lipooligosaccharide (LOS), and Pam3CSK, which is a known TLR2 ligand.
Production of two cytokines, IL-6 and TNFα, was then measured using ELISA. PorB
stimulation proved to be the most effective stimulus of TNFα and IL-6 production
compared to LOS and Pam3CSK. Inhibiting the c-Jun N-terminal kinase (JNK) pathway
led to non-detectable levels of both TNFα and IL-6 in cells with all treatments. The
inhibition of the extracellular signal-regulated kinase (ERK.) pathway also led to
decreased levels of IL-6 and TNFα but only in PorB stimulated BMDMs. This suggests
that the JNK and ERK. pathways play significant roles in the induction of IL-6 and TNFα
via TLR2 signaling. Further investigation can be carried out to better determine the
specific signaling events that occur in the JNK and ERK. pathways following stimulation
with PorB to better understand its potency as an adjuvant.
With honors.
With honors.
Description
v, 36 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.