Lutein inhibits IL‑6 expression by inducing PPAR‑γ activation and SOCS3 expression in cerulein‑stimulated pancreatic acinar cells

Ahn,Yu Jin; Lim,Joo Weon; Kim,Hyeyong

doi:10.3892/mmr.2022.12818

Lutein inhibits IL‑6 expression by inducing PPAR‑γ activation and SOCS3 expression in cerulein‑stimulated pancreatic acinar cells

Authors:
- Yu Jin Ahn
- Joo Weon Lim
- Hyeyong Kim
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Affiliations: Department of Food and Nutrition, College of Human Ecology, Yonsei University, Seoul 03722, Republic of Korea
Published online on: August 9, 2022 https://doi.org/10.3892/mmr.2022.12818
Article Number: 302
Copyright: © Ahn et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute pancreatitis is a severe inflammatory disease of the pancreas. In experimental acute pancreatitis, cerulein induces the expression of interleukin‑6 (IL‑6) by activating Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 in pancreatic acinar cells. Ligands of peroxisome proliferator activated receptor‑γ (PPAR‑γ) and suppressor of cytokine signaling (SOCS) 3 inhibit IL‑6 expression by suppressing JAK2/STAT3 in cerulein‑stimulated pancreatic acinar AR42J cells. Lutein, an oxygenated carotenoid, upregulates and activates PPAR‑γ to regulate inflammation in a renal injury model. The present study aimed to determine whether lutein activated PPAR‑γ and induced SOCS3 expression in unstimulated AR42J cells, and whether lutein inhibited activation of JAK2/STAT3 and IL‑6 expression via activation of PPAR‑γ and SOCS3 expression in cerulein‑stimulated AR42J cells. The anti‑inflammatory mechanism of lutein was determined using reverse transcription‑quantitative PCR, western blot analysis and enzyme‑linked immunosorbent assay in AR42J cells stimulated with or without cerulein. In another experiment, cells were treated with lutein and the PPAR‑γ antagonist GW9662 or the PPAR‑γ agonist troglitazone prior to cerulein stimulation to determine the involvement of PPAR‑γ activation. The results indicated that lutein increased PPAR‑γ and SOCS3 levels in unstimulated cells. Cerulein increased phospho‑specific forms of JAK2 and STAT3, and mRNA and protein expression of IL‑6, but decreased SOCS3 levels in AR42J cells. Cerulein‑induced alterations were suppressed by lutein or troglitazone. GW9662 alleviated the inhibitory effect of lutein on JAK2/STAT3 activation and IL‑6 expression in cerulein‑stimulated cells. In conclusion, lutein inhibited the activation of JAK2/STAT3 and reduced IL‑6 levels via PPAR‑γ‑mediated SOCS3 expression in pancreatic acinar cells stimulated with cerulein.

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