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Metformin alleviates LTA-induced inflammatory response through PPARγ/MAPK/NF-κB signaling pathway in bovine mammary epithelial cells
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作者 ABDELAZIZ ADAM IDRISS ARBAB CHUNQING YIN +6 位作者 xubin lu YAN LIANG ISMAIL MOHAMED ABDALLA AMER ADAM IDRIS TIANLE XU YONGJIANG MAO ZHANGPING YANG 《BIOCELL》 SCIE 2022年第11期2443-2454,共12页
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 induc... 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 100μg/mL significantly stimulated the MAPK14,IL-6 and IL-1βmRNA 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 PPARγphosphorylation by up-regulating the expression of PPARγin 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 PPARγactivation.These results suggested that metformin could function as an anti-inflammatory drug in the treatment of mastitis. 展开更多
关键词 METFORMIN LTA Primary bovine mammary epithelial cell Anti-inflammatory effect PPARΓ Nuclear factor-κB Mitogen-activated protein kinase
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