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ARTICLE
Metformin alleviates LTA-induced inflammatory response through PPARγ/MAPK/NF-κB signaling pathway in bovine mammary epithelial cells
ABDELAZIZ ADAM IDRISS ARBAB1,3,#, CHUNQING YIN4,#, XUBIN LU1, YAN LIANG1, ISMAIL MOHAMED ABDALLA1, AMER ADAM IDRIS3, TIANLE XU1,2, YONGJIANG MAO1, ZHANGPING YANG1,2,*
1 College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China
2 Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Yangzhou University, Yangzhou, 225009, China
3 Biomedical Research Institute, Darfur College, Nyala, 63313, Sudan
4 Shandong Haiding husbandry Co., Ltd, Jinan, 250100, China
* Corresponding Author: Zhangping Yang,
# These authors contributed equally for this work
(This article belongs to the Special Issue: Decoding Gene (including circRNA, lincRNA miRNA and mRNA) Expression)
BIOCELL 2022, 46(11), 2443-2454. https://doi.org/10.32604/biocell.2022.020865
Received 16 December 2021; Accepted 11 February 2022; Issue published 07 July 2022
Abstract
Mastitis is a common inflammatory cow mammary infection; that causes significant economic loss in dairy
industry. Given the interesting connection between metformin’s anti-inflammatory function and mastitis model
induced by LTA in pbMECs, our objective was to prove that metformin was beneficial in suppressing
proinflammatory response induced by LTA through modulation of mitogen-activated protein kinase (MAPK) and
nuclear factor kappa B (NF-κB) signaling pathways and activation of peroxisome proliferator-activated receptor-γ
(PPARγ) in pbMECs. The proliferation of cells and mRNA expression were measured using EdU assay and
quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Immunoblotting and immunofluorescence
analysis were conducted to evaluate the expression of target proteins in inflammatory and anti-inflammatory
responses to metformin and LTA. Finally, pbMECs were allowed to treat with the PPAR antagonist GW9662, and
inflammatory markers were detected in the cells. Our results showed that LTA concentration at 100 µg/mL
significantly stimulated the MAPK14, IL-6 and IL-1β mRNA expressions compared to the control cells (
P < 0.05) in
dose-dependent tests for LTA. Metformin suppressed the phosphorylation expressions of MAPK (ERK1/2, p38, and
JNK) in LTA-stimulated pbMECs. Metformin also reduced the protein expression of NF-κB, interleukin-8 (IL-8),
interleukin-1β (IL-1β) and interleukin-6 (IL-6) in pbMECs pretreated with LTA. Metformin administration activated
PPARγ phosphorylation by up-regulating the expression of PPARγ in LTA-stimulated pbMECs. Treatment with
GW9662 resulted in increased IL-6 expression, which was reversed by metformin. These findings collectively
indicated that metformin act to attenuate LTA-stimulated inflammatory response in pbMECs by suppressing MAPK
and NF-κB activation via a mechanism partially dependent on PPARγ activation. These results suggested that
metformin could function as an anti-inflammatory drug
Keywords
Cite This Article
APA Style
ARBAB, A.A.I., YIN, C., LU, X., LIANG, Y., ABDALLA, I.M. et al. (2022). Metformin alleviates lta-induced inflammatory response through PPARγ/MAPK/NF-κB signaling pathway in bovine mammary epithelial cells. BIOCELL, 46(11), 2443-2454. https://doi.org/10.32604/biocell.2022.020865
Vancouver Style
ARBAB AAI, YIN C, LU X, LIANG Y, ABDALLA IM, IDRIS AA, et al. Metformin alleviates lta-induced inflammatory response through PPARγ/MAPK/NF-κB signaling pathway in bovine mammary epithelial cells. BIOCELL . 2022;46(11):2443-2454 https://doi.org/10.32604/biocell.2022.020865
IEEE Style
A.A.I. ARBAB et al., "Metformin alleviates LTA-induced inflammatory response through PPARγ/MAPK/NF-κB signaling pathway in bovine mammary epithelial cells," BIOCELL , vol. 46, no. 11, pp. 2443-2454. 2022. https://doi.org/10.32604/biocell.2022.020865