MAP Kinase Inhibition Prevents Induction of IL-6 and TNFα by Porin B of Neisseria meningitidis in Murine Macrophages

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, respectively. •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 adjuvant