4.7 Article

The Patatin-Like Phospholipase Domain Containing Protein 7 Regulates Macrophage Classical Activation through SIRT1/NF-κB and p38 MAPK Pathways

Journal

Publisher

MDPI
DOI: 10.3390/ijms232314983

Keywords

classical macrophage activation; PNPLA7; SIRT1; NF-kappa B; p38 MAPK

Funding

  1. National Nature Science Foundation of China
  2. Chongqing Science and Technology Bureau
  3. [31801139]
  4. [cstc2020jcyj-mxsmX0007]
  5. [CSTB2022NSCQ-MSX0957]

Ask authors/readers for more resources

Phospholipase PNPLA7 suppresses M1 polarization of LPS-challenged macrophages by modulating SIRT1/NF-κ B and p38 MAPK-dependent pathways.
Lysophosphatidylcholine (LPC) is a bioactive lipid that modulates macrophage polarization during immune responses, inflammation, and tissue remodeling. Patatin-like phospholipase domain containing protein 7 (PNPLA7) is a lysophospholipase with a preference for LPC. However, the role of PNPLA7 in macrophage polarization as an LPC hydrolase has not been explored. In the current study, we found that PNPLA7 is highly expressed in naive macrophages and downregulated upon lipopolysaccharide (LPS)-induced polarization towards the classically activated (M1) phenotype. Consistently, overexpression of PNPLA7 suppressed the expression of proinflammatory M1 marker genes, including interleukin 1 beta (IL-1 beta), IL-6, inducible nitric oxide synthase (iNOS), and tumor necrosis factor alpha (TNF-alpha), whereas knockdown of PNPLA7 augmented the inflammatory gene expression in LPS-challenged macrophages. PNPLA7 overexpression and knockdown increased and decreased Sirtuin1 (SIRT1) mRNA and protein levels, respectively, and affected the acetylation of the nuclear factor-kappa B (NF-kappa B) p65 subunit, a key transcription factor in M1 polarization. In addition, the levels of phosphorylated p38 mitogen-activated protein kinase (MAPK) were suppressed and enhanced by PNPLA7 overexpression and knockdown, respectively. Taken together, these findings suggest that PNPLA7 suppresses M1 polarization of LPS-challenged macrophages by modulating SIRT1/NF-kappa B- and p38 MAPK-dependent pathways.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available