S. aureus haemolysin A-induced IL-8 and IL-6 release from human airway epithelial cells is mediated by activation of p38- and Erk-MAP kinases and additional, cell type-specific signalling mechanisms.
Soluble virulence-associated factors of Staphylococcus aureus like haemolysin A (Hla) induce secretion of chemo/cytokines from airway epithelial cells. To elucidate the potential roles of specific signalling pathways in this response, we treated 16HBE14o-, S9 or A549 cells with recombinant Hla (rHla). In a dose-dependent manner, rHla induced secretion of IL-8 in all three cell types, but IL-6 release only in 16HBE14o- and S9 cells. rHla-mediated secretion of IL-8 and IL-6 was suppressed by pre-incubation of cells with inhibitors of Erk type or p38 MAP kinases, indicating that activation of these signalling pathways is essential for IL-8 release in all three cell types and for IL-6 release in 16HBE14o- and S9 cells. The rHla-mediated phosphorylation and activation of p38 MAP kinase seem to depend on elevations in [Ca(2+)]i, an early response in rHla-treated cells. Inhibitors of calmodulin or calcium/calmodulin-dependent kinase II attenuated rHla-mediated release of IL-8 in 16HBE14o- and A549 cells and of IL-6 in 16HBE14o- cells. This indicates that rHla may mediate simultaneous activation of calmodulin-dependent processes as additional prerequisites for chemo/cytokine secretion.However, the inhibitors of calmodulin-dependent signalling did not affect rHla-induced p38 MAP kinase phosphorylation, indicating that this pathway works in parallel with p38 MAP kinase.
Animal Physiology and Biochemistry, Zoological Institute, Ernst Moritz Arndt University, Johann Sebastian Bach-Strasse 11/12, D-17487 Greifswald, Germany.
Susann
S
Räth
Sabine
S
Ziesemer
Amelie
A
Witte
Anne
A
Konkel
Christian
C
Müller
Petra
P
Hildebrandt
Uwe
U
Völker
Jan-Peter
JP
Hildebrandt
D001427:Bacterial Toxins / Q000276:immunology*; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006460:Hemolysin Proteins / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D013211:Staphylococcus aureus / Q000276:immunology
D001427:Bacterial Toxins; C508606:CXCL8 protein, human; D006460:Hemolysin Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C021091:staphylococcal alpha-toxin; D048049:Extracellular Signal-Regulated MAP Kinases