Pseudomonas aeruginosa-Derived DnaJ Induces the Expression of IL−1β by Engaging the Interplay of p38 and ERK Signaling Pathways in Macrophages
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Published:2023-11-03
Issue:21
Volume:24
Page:15957
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Kim Dae-Kyum12ORCID, Huh Jin-Won1ORCID, Yu Hyeonseung1, Lee Yeji1, Jin Yongxin3, Ha Un-Hwan12ORCID
Affiliation:
1. Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, Republic of Korea 2. Interdisciplinary Graduate Program for Artificial Intelligence Smart Convergence Technology, Korea University, Sejong 30019, Republic of Korea 3. State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, Nankai University, Tianjin 300071, China
Abstract
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.
Funder
National Research Foundation of Korea
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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