Porins fromSalmonella entericaSerovar Typhimurium Activate the Transcription Factors Activating Protein 1 and NF-κB through the Raf-1-Mitogen-Activated Protein Kinase Cascade

Abstract

In this study we examined the ability of Salmonella enterica serovar Typhimurium porins to activate activating protein 1 (AP-1) and nuclear factor B (NF- B

Investigation into the interaction of the bacterial protease OmpT with outer membrane lipids and biological activity of OmpT:lipopolysaccharide complexes

“…Furthermore, neither the presence of serum nor CD14 influenced this activity, only the presence of the integrins CD11a/CD18 exhibited a slight influence. Investigations into the early responses after porin stimulation showed that the cellsignalling pathways include activating protein 1 (AP1) and nuclear factor jB (NF-jB) through the mitogenactivated protein kinase (MAPK) cascade (Galdiero et al 2002). The authors found differences in the signalling by LPS because the cytokine release after stimulation with porins began after 2 h and lasted for 5-6 h, whereas the release after LPS stimulation started after 30 min and decreased after 2 h. The authors also tested the porin preparations for LPS contamination by applying the Limulus test as well as polymyxin B to remove LPS, but found no evidence for a contamination.…”

“…Thus, LPS is known to be one of the most potent stimuli of the immune system. Furthermore, it was found that porins may also stimulate cytokines such as interleukins and tumour necrosis factor a (Galdiero et al 1993(Galdiero et al , 2001(Galdiero et al , 2002Alurkar and Kamat 1997;Massari et al 2002).…”

Septic Shock by Gram-Negative Infections: Role of Outer Membrane Proteins

“…Neisserial porins induce nuclear translocation of the transcription factor NF-κB in B cells and dendritic cells that was maximal by 3 h of stimulation (Massari, 2003). S. enterica serovar typhimurium porins also activate AP-1 and NF-κB in U937 cells involving the Raf-1-MEK1/2-MAPK pathways (Galdiero, 2002); pretreatment with PD-098059 and with SB-203580 markedly affected the activation, indicating that the p38 signaling pathway is mainly involved in AP-1 and NF-κB activation. In contrast, forskolin pretreatment did not block transcription factor activation by porins, suggesting that a Raf-1-independent pathway may also be involved following porin stimulation.…”

“…Neisserial porins induce protein tyrosine phosphorylation and alter the surface expression of the co-stimulatory molecule B7-2 (Massari, 2003). Recent evidence suggests that the Raf-1-MEK1/2-MAPK pathways are included among the proteins which are phosphorylated following porin stimulation (Galdiero, 2002). The use of some specific inhibitors of phosphorylation pathways such as SB-203580 (p38 inhibitor), PD-098059 (MEK/ERK kinase inhibitor) and forskolin (Raf-1 inhibitor) demonstrated that they modulate in a different way cytokine mRNA expression in cells stimulated with porins.…”

Proinflammatory signal transduction pathway induced by Shigella flexneri porins in caco-2 cells

“…NFκB activation in intestinal epithelial cells is mediated by acknowledgment between bacterial products and a family of transmembrane receptors termed Toll-like receptors (TLRs). These receptors are called pattern-recognition receptors because they recognize repetitive patterns, i.e., pathogen-associated molecular patterns (PAMPs), present in several microorganisms including Gram-positive and Gramnegative bacteria, fungi and mycobacteria (11,18). The interaction of TLRs with PAMPs results in the activation of multiple intracellular signaling events such as the activation of NF-κB and the production of cytokines (8,24,28).…”