bims-inflin Biomed News
on Inflammasome and infection
Issue of 2023‒11‒19
two papers selected by
Juliane Cristina Ribeiro Fernandes, Faculdade de Medicina de Ribeirão Preto
  1. Pseudomonas aeruginosa-Derived DnaJ Induces the Expression of IL-1β by Engaging the Interplay of p38 and ERK Signaling Pathways in Macrophages.
  2. Phillyrin ameliorates influenza a virus-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation.
  1. Int J Mol Sci. 2023 Nov 03. pii: 15957. [Epub ahead of print]24(21):
    Pseudomonas aeruginosa-Derived DnaJ Induces the Expression of IL-1β by Engaging the Interplay of p38 and ERK Signaling Pathways in Macrophages.
    Dae-Kyum Kim, Jin-Won Huh, Hyeonseung Yu, Yeji Lee, Yongxin Jin, Un-Hwan Ha.
      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.
    Keywords:  HSP40 homolog; IL−1β; MAPK; NF-κB; inflammasome
    DOI:  https://doi.org/10.3390/ijms242115957
  2. Virol J. 2023 Nov 13. 20(1): 262
    Phillyrin ameliorates influenza a virus-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation.
    Shanyu Zhang, Fengzhi Sun, Jinlu Zhu, Jianhong Qi, Wenjing Wang, Ziming Liu, Wenqian Li, Chuanguo Liu, Xuehuan Liu, Nonghan Wang, Xinyu Song, Dan Zhang, Dongmei Qi, Xiaolong Wang.
      Influenza is an acute viral respiratory illness with high morbidity rates worldwide. Excessive pulmonary inflammation is the main characteristic of lethal influenza A virus (IAV) infections. Therapeutic options for managing influenza are limited to vaccines and some antiviral medications. Phillyrin is one of the major bioactive components of the Chinese herbal medicine Forsythia suspensa, which has the functions of sterilization, heat clearing and detoxification. In this work, the effect and mechanism of phillyrin on H1N1 influenza (PR8)-induced pneumonia were investigated. We reported that phillyrin (15 mg/kg) treatment after viral challenge significantly improved the weight loss, ameliorated pulmonary inflammation and inhibited the accumulation of multiple cytokines and chemokines in bronchoalveolar lavage fluid on 7 days post infection (dpi). In vitro, phillyrin suppressed influenza viral replication (Matrixprotein and nucleoprotein messenger RNA level) and reduced influenza virus-induced cytopathic effect (CPE). Furthermore,chemokine receptor CXCR2 was confirmed to be markedly inhibited by phillyrin. Surface plasmon resonance results reveal that phillyrin exhibits binding affinity to CXCR2, having a binding affinity constant (KD) value of 1.858e-5 M, suggesting that CXCR2 is a potential therapeutic target for phillyrin. Moreover, phillyrin inhibited the mRNA and protein expression levels of Caspase1, ASC and NLRP3 in the lungs of mice with H1N1-induced pneumonia.This study reveals that phillyrin ameliorates IAV-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation partly.
    Keywords:  CXCR2; Influenza; NLRP3; Phillyrin; Pulmonary inflammation
    DOI:  https://doi.org/10.1186/s12985-023-02219-4
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