MiR-499 enhances Porphyromonas gingivalis LPS-induced inflammatory response in macrophages by targeting NRIP1 via

Chuanmin Wang1, Xiangxin Li

  • 1Department of Stomatology, The First People's Hospital of Lianyungang, Lianyungang 222061, Jiangsu, China.

Journal of Biosciences
|December 4, 2023
PubMed

Insights

MicroRNA miR-499 promotes inflammation in macrophages by targeting NRIP1 and activating the JAK/STAT pathway. This study clarifies miR-499

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • MicroRNAs (miRNAs) are crucial regulators of immune cell activity and development.
  • miR-499 plays a significant role in immune cell function, but its precise mechanism in regulating inflammatory responses is not fully understood.
  • Macrophages are key players in the inflammatory response.

Purpose of the Study:

  • To investigate the role of microRNA miR-499 in regulating the inflammatory response in macrophages.
  • To elucidate the molecular mechanism by which miR-499 influences macrophage inflammation, including its interaction with NRIP1 and the JAK/STAT pathway.

Main Methods:

  • Utilized RAW 264.7 macrophages as a cell model.
  • Stimulated macrophages with Porphyromonas gingivalis lipopolysaccharide (LPS).
  • Quantified miR-499 and inflammatory cytokine (IL-6, IL-1β, TNF-α) expression using qRT-PCR and ELISA.
  • Predicted and validated miR-499 binding sites on NRIP1 mRNA using StarBase and qRT-PCR.
  • Assessed the JAK/STAT pathway activation by measuring phosphorylated JAK2 and STAT1 levels via Western blotting.
  • Employed miR-499 inhibitors and sh-NRIP1 to evaluate regulatory effects.

Main Results:

  • P. gingivalis LPS stimulation led to increased miR-499 expression and promoted macrophage inflammatory response.
  • miR-499 directly targets the NRIP1 3' UTR, negatively regulating NRIP1 mRNA expression.
  • miR-499 positively correlated with inflammatory cytokine expression (IL-6, IL-1β, TNF-α) and negatively correlated with NRIP1 expression.
  • miR-499 activation of the JAK/STAT pathway (p-JAK2, p-STAT1) was mediated through NRIP1 regulation.

Conclusions:

  • miR-499 significantly regulates the P. gingivalis LPS-induced inflammatory response in macrophages.
  • The mechanism involves miR-499 targeting NRIP1, thereby modulating inflammatory cytokine production.
  • miR-499 activates the JAK/STAT signaling pathway through NRIP1 regulation, contributing to the inflammatory process.

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