|dc.description.abstract||•Neisseria meningitidis is a Gram negative pathogenic bacteria
responsible for bacterial meningitis and sepsis. During infection the
bacteria release lipooligosaccharide (LOS), a component of the outer
membrane of the bacteria. These components then activate the cells of
the immune system through a variety of receptor molecules.
•As signaling continues downstream of the TLRs the mitogen-activated
protein kinases (MAPKs) become involved through a phosphorylation
cascade. MAPKs are responsible for regulating mitosis, apoptosis, cell
movement, metabolism, and gene expression.
•There are three principle MAPK subfamilies including the extracellular
signal-regulated kinases (ERK), the c-Jun-NH2-terminal kinases (JNK),
and p38 enzymes.
•Ultimately, a group of intercellular signaling molecules called cytokines
are activated. Of particular interest are the pro-inflammatory cytokines
TNFa and IL-6, which have been found to regulate apoptosis during
infection in addition to regulating antibody production in B cells,
•Porins, small pore molecules covering the surface of the bacterial cell
membrane have also become of interest because of the implication of
neisserial porin as a potent immune adjuvant.
•Through looking at the effects of MAPK inhibitors on cytokine production
in murine macrophage cells stimulated with different TLR ligands (LOS,
neisserial porin B (PorB), and Pam3CSK) this study will elucidate more
of the signaling events that lead to the efficacy of PorB as a potent