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 Ca²⁺]_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.