title: The UII/UT system mediates upregulation of proinflammatory cytokines through p38 MAPK and NF-κB pathways in LPS-stimulated Kupffer cells.
abstract: The urotensin II (UII)/UII receptor (UT) system is closely related to immune inflammation. In acute liver failure (ALF), the UII/UT system can promote the production and release of proinflammatory cytokines, inducing an inflammatory injury response in liver tissue. However, the mechanism by which the hepatic UII/UT system promotes proinflammatory cytokine production and release is not clear. To solve this problem, we used primary Kupffer cells (KCs) as the model system in the current study. The results showed that after lipopolysaccharide (LPS) stimulation, KCs showed significantly increased expression and release of UII/UT and proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Pretreatment with urantide, which is a UT receptor antagonist, significantly inhibited the LPS-stimulated expression and release of UII/UT, TNF-α, and IL-1β by KCs. In addition, LPS stimulation induced nuclear p38 mitogen-activated protein kinase (MAPK) protein phosphorylation and expression of the nuclear nuclear factor κB (NF-κB) p65 subunit in KCs and enhanced the binding activity of NF-κB to DNA molecules, whereas urantide pretreatment significantly inhibited the LPS-stimulated nuclear expression and activity of these molecules in KCs. Therefore, our conclusion is that the UII/UT system mediates LPS-stimulated production and release of proinflammatory cytokine by KCs, and this mediating effect at least partially relies on the inflammatory signaling pathway molecules p38 MAPK and NF-κB.
authors: Department of Hepatology, Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiaotong University, Shanghai, China.
authors: Liang Ming
authors: LM
authors: Liu
authors: Department of Hepatology, Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiaotong University, Shanghai, China.
authors: Dong Yu
authors: DY
authors: Liang
authors: Department of Hepatology, Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiaotong University, Shanghai, China.
authors: Chang Gen
authors: CG
authors: Ye
authors: Department of Hepatology, Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiaotong University, Shanghai, China.
authors: Wen Juan
authors: WJ
authors: Tu
authors: Department of Hepatology, Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiaotong University, Shanghai, China.
authors: Tong
authors: T
authors: Zhu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D053583:Interleukin-1beta / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014579:Urotensins / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D016207:Cytokines; D017931:DNA Primers; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; D014579:Urotensins; C473142:Uts2r protein, rat; C492079:urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-; C029677:urotensin II