Open Access

HIPK2 sustains inflammatory cytokine production by promoting endoplasmic reticulum stress in macrophages

  • Authors:
    • Long Xu
    • He Fang
    • Dayuan Xu
    • Guangyi Wang
  • View Affiliations

  • Published online on: October 9, 2020     https://doi.org/10.3892/etm.2020.9301
  • Article Number: 171
  • Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Uncontrolled inflammatory cytokine production by macrophages contributes to numerous conditions, including infection, endotoxemia and sepsis. A previous study proposed that endoplasmic reticulum (ER) stress acts as an essential process in inflammatory cytokine production by macrophages. The present study used a mouse sepsis model and in vitro macrophages to demonstrate that homeodomain‑interacting protein kinase 2 (HIPK2) sustained cytokine production in an ER stress‑dependent manner. HIPK2 expression was upregulated in the early phase of lipopolysaccharide stimulation. HIPK2 knockdown attenuated IL‑6 and TNF‑α production, and p65 phosphorylation in macrophages. Furthermore, the attenuated cytokine production was abolished by the ER stress agonist tunicamycin. The activation of ER stress increased the levels of IL‑6 and TNF‑α, and the phosphorylation of p65, in macrophages following knockdown of HIPK2. Furthermore, HIPK2 inhibition attenuated the production of IL‑6 and TNF‑α in vitro and in vivo. Therefore, HIPK2 sustained inflammatory cytokine production by promoting ER stress in macrophages. Targeting HIPK2 may be a potential strategy for the management of uncontrolled inflammation in clinical settings.
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December-2020
Volume 20 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Xu L, Fang H, Xu D and Wang G: HIPK2 sustains inflammatory cytokine production by promoting endoplasmic reticulum stress in macrophages. Exp Ther Med 20: 171, 2020
APA
Xu, L., Fang, H., Xu, D., & Wang, G. (2020). HIPK2 sustains inflammatory cytokine production by promoting endoplasmic reticulum stress in macrophages. Experimental and Therapeutic Medicine, 20, 171. https://doi.org/10.3892/etm.2020.9301
MLA
Xu, L., Fang, H., Xu, D., Wang, G."HIPK2 sustains inflammatory cytokine production by promoting endoplasmic reticulum stress in macrophages". Experimental and Therapeutic Medicine 20.6 (2020): 171.
Chicago
Xu, L., Fang, H., Xu, D., Wang, G."HIPK2 sustains inflammatory cytokine production by promoting endoplasmic reticulum stress in macrophages". Experimental and Therapeutic Medicine 20, no. 6 (2020): 171. https://doi.org/10.3892/etm.2020.9301