The Pseudomonas aeruginosa HSP70-like protein DnaK induces IL-1ß expression via TLR4-dependent activation of the NF-κB and JNK signaling pathways.

ABSTRACT

IL-1ß expression is increased in response to P. aeruginosa infection, but the responsible proteins have not been clearly elucidated. Here, we demonstrate for the first time that IL-1ß expression is induced in response to the heat shock protein 70-like protein DnaK. Treatment with recombinant DnaK (rDnaK) increased IL-1ß expression in a dose- and time-dependent manner, and the release of mature IL-1ß in response to rDnaK was detected to an extent similar to that stimulated by the well-known agonists, lipopolysaccharide and nigericin. rDnaK-mediated IL-1ß expression was driven by the NF-κB signaling pathway. In addition, expression was controlled by the JNK signaling pathway, although these two signaling cascades act independently upon rDnaK stimulation. Finally, rDnaK-induced IL-1ß expression was initiated via the action of TLR4. Taken together, the data reveal that P. aeruginosa-derived DnaK induces expression of IL-1ß via TLR4-dependent activation of the NF-κB and JNK signaling pathways.