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Pseudomonas aeruginosa-Derived DnaJ Induces the Expression of IL−1β 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 regula...

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Detalles Bibliográficos
Autores principales: Kim, Dae-Kyum, Huh, Jin-Won, Yu, Hyeonseung, Lee, Yeji, Jin, Yongxin, Ha, Un-Hwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10648868/
https://www.ncbi.nlm.nih.gov/pubmed/37958940
http://dx.doi.org/10.3390/ijms242115957
Descripción
Sumario: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−1β expression in macrophages. We demonstrated that DnaJ modulates macrophages to secrete IL−1β by activating NF-κB and MAPK signaling pathways. Specifically, ERK was identified as a positive mediator for IL−1β 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−1β 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−1β production from DnaJ-treated macrophages. These findings emphasize the importance of understanding the signaling mechanisms underlying IL−1β induction and suggest the potential utility of DnaJ as an adjuvant for stimulating inflammasome activation.