Clostridium perfringens alpha-toxin induces the release of IL-8 through a dual pathway via TrkA in A549 cells

Hemoglobin Receptor Protein from Porphyromonas gingivalis Induces Interleukin-8 Production in Human Gingival Epithelial Cells through Stimulation of the Mitogen-Activated Protein Kinase and NF-κB Signal Transduction Pathways

“…Interestingly, in contrast to our results, p38 MAPK has been shown to mediate ATF-2 phosphorylation in VacA-stimulated AZ521 cells (56). Additionally, C. perfringens alpha-toxin induces the production of IL-8 by Erk1/2/NF-B-p65 and p38 MAPK pathways in A549 cells (43). Moreover, activation of Erk and p38, but not participation of JNK, was also observed in Moraxella catarrhalis-induced IL-8 production by epithelial cells (57).…”

“…Numerous studies have reported that infection of epithelial cells with bacterial pathogens, including Salmonella enterica serovar Typhimurium (37,38), Helicobacter pylori (16,39,40), enterohemorrhagic E. coli (41), enteropathogenic E. coli (42), and Clostridium perfringens (43), results in the release of IL-8 through the activation of MAPK pathways.…”

Clostridium perfringens Alpha-toxin Recognizes the GM1a-TrkA Complex

“…Mean values among experimental groups were compared using Student's t test, and p Ͻ 0.01 was considered statistically significant. (19). To investigate the effect of gangliosides and sialic acid on the binding of alpha-toxin to A549 cells and on the release of IL-8, the cells were treated with various concentrations of PPMP, which is a ganglioside synthase inhibitor, or neuraminidase from C. perfringens, which catalyzes the hydrolysis of terminal sialic acid residues, at 37°C for 4 days or 60 min, respectively.…”

“…We also reported that alpha-toxin simultaneously induced the formation of diacylglycerol through the activation of endogenous PLC and phosphorylation of ERK1/2, NFB, and p38MAPK via activation of tyrosine kinase A (TrkA) in human lung adenocarcinoma epithelial cell line (A549) cells and that these events induced the release of interleukin-8 (IL-8) (19). In addition, the toxin-induced release of TNF-␣ was found to be dependent on the activation of ERK1/2 signal transduction via the phosphorylation of TrkA in neutrophils and macrophages (13).…”

Bacterial Sphingomyelinases and Phospholipases as Virulence Factors

“…perfringens alpha-toxin induces the respiratory burst in neutrophils by inducing the activation of PKC via two separate pathways: elevation of DAG generated by activation of an endogenous PLC through a pertussis toxin-sensitive GTP-binding protein, and activation of a tropomyosin-related kinase receptor (TrkA receptor) that leads to PDK1 phosphorylation (225,226). In epithelial cells, alpha-toxin binding to GM1a ganglioside induces TNF-␣ and IL-8 production through the activation of the TrkA receptor and the p38 mitogen-activated protein kinase (MAPK) pathway, as well as a PLC-␥1, ERK1/2-NF-B-dependent pathway (232)(233)(234). TNF-␣ plays an important role in the toxic effect of alpha-toxin, since the administration of specific antibodies against TNF-␣ protects mice from its lethal effect (235).…”