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IGF2BP1 Promotes LPS-induced NFκB Activation and Pro-Inflammatory Cytokines Production in Human Macrophages and Monocytes

IGF2BP1 Promotes LPS-induced NFκB Activation and Pro-Inflammatory Cytokines Production in Human Macrophages and Monocytes

Jing Xie, Quan Li, Xing-Hao Zhu, Yunyun Gao, Wang-Hong Zhao

Biochem Biophys Res Commun. 2019 Jun 11;513(4):820-826.

PMID: 31000200

Abstract:

Background:
Lipopolysaccharide (LPS)-induced macrophage/monocyte activation and pro-inflammatory cytokines production are important mediators for periodontitis progression. The current study tested the potential role of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in the process.
Methods:
THP-1 human macrophages and primary human peripheral blood mononuclear cells (PBMCs) were treated with LPS. mRNA and protein expression of IGF2BP1 were tested by qPCR and Western blotting assay. IGF2BP1 expression was altered by shRNAs or CRISPR/Cas-9 gene editing methods. LPS-induced cytokine production was tested by ELISA assay. Cytokine mRNA expression was tested by the quantitative real-time reverse transcriptase polymerase chain reaction (qPCR) assay.
Results:
In THP-1 human macrophages and PBMCs, treatment with LPS induced mRNA and protein expression of IGF2BP1. IGF2BP1 silencing (by targeted shRNAs) or CRISPR/Cas-9 knockout largely inhibited LPS-induced production of multiple pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6. Conversely, forced over-expression of IGF2BP1 facilitated LPS-induced pro-inflammatory cytokines production in THP-1 cells. For the mechanism study, we show that IGF2BP1 co-immunoprecipitated with p65-p52 nuclear factor kappa B (NFκB) complex in nuclei of LPS-treated THP-1 cells. Significantly, LPS-induced p65-p52 nuclear translocation and NFκB activation were inhibited by IGF2BP1 silencing or CRISPR/Cas-9 knockout.
Conclusion:
IGF2BP1 promotes LPS-induced NFκB signalling and transcriptional activation in human macrophages and monocytes.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413303	IGF-Binding Protein 1 human			Price

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