MAP Kinase Inhibition Prevents Induction of IL-6 and TNFα by Porin B of Neisseria meningitidis in Murine Macrophages
Jorth, Peter Allan
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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.