Pseudomonas aeruginosa-Derived DnaJ Induces the Expression of IL-1 by Engaging the Interplay of p38 and ERK Signaling Pathways in Macrophages

As members of pathogen-associated molecular patterns, bacterial heat shock proteins (HSPs) are widely recognized for their role in initiating innate immune responses. This study aimed to examine the impact of DnaJ, a homolog of HSP40 derived from Pseudomonas aeruginosa (P. aeruginosa), on the regulation of IL-1 beta expression in macrophages. We demonstrated that DnaJ modulates macrophages to secrete IL-1 beta by activating NF-kappa B and MAPK signaling pathways. Specifically, ERK was identified as a positive mediator for IL-1 beta expression, while p38 acted as a negative mediator. These results suggest that the reciprocal actions of these two crucial MAPKs play a vital role in controlling IL-1 beta expression. Additionally, the reciprocal actions of MAPKs were found to regulate the activation of inflammasome-related molecules, including vimentin, NLRP3, caspase-1, and GSDMD. Furthermore, our investigation explored the involvement of CD91/CD40 in ERK signaling-mediated IL-1 beta production from DnaJ-treated macrophages. These findings emphasize the importance of understanding the signaling mechanisms underlying IL-1 beta induction and suggest the potential utility of DnaJ as an adjuvant for stimulating inflammasome activation.