| Summary: | Lumei Liu,1,* Meng Wang,1,* Menglu Guo,2,* Li Xian,3,* Jixiang Xu,1 Dehai Xian,4 Jianqiao Zhong1 1Department of Dermatology, the Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Dermatology, the People’s Hospital of Leshan, Southwest Medical University, Leshan, 614003, People’s Republic of China; 3Department of Emergency, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 4Department of Neurobiology, Southwest Medical University, Luzhou, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianqiao Zhong, Department of Dermatology, the Affiliated Hospital, Southwest Medical University, No. 25 Tai Ping Jie, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86-15082088598, Fax +86-830-3198173, Email zjq7632@hotmail.com Dehai Xian, Department of Neurobiology, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +86-18008203056, Email dh969@163.comBackground: Immune-mediated inflammation and oxidative stress play pivotal roles in Henoch-Schonlein purpura (HSP), primarily through the TLR4/MyD88/NF-κB pathway. Proanthocyanidins (PCs) exert anti-inflammatory and antioxidant effects by regulating some signals like TLR4/MyD88/NF-κB. Previous research uncovered that PCs could alleviate purpura-like lesions and pathological changes on rats likely through attenuating inflammation and OS damage. The mechanism of PCs on HSP deserves further investigation.Objective: To clarify the potential mechanism of PCs to HUVECs induced by the serum of HSP patients.Methods: HUVECs were randomly divided into blank, control, model, and low-, medium-, and high-concentration PCs group. Then, 25% HSP serum was assigned to the latter four groups, while 25% serum from healthy subjects to control group and serum-free culture medium to blank one. The last three groups separately received different concentrations of PCs. In addition, TAK-242, a TLR4 inhibitor, was applied to investigate the effect of TLR4-related signals in PCs against HSP serum-induced damage. Finally, inflammatory and OS-related parameters were detected by using cytological/molecular-biological techniques.Results: Treated with HSP serum later, the levels of immuno-inflammatory and oxidative indicators obviously went up (P < 0.05), and those of antioxidants remarkably went down (P < 0.05). PCs, however, reversed above phenomena (P < 0.05). Moreover, TLR4, MyD88 and NF-κB proteins/genes highly expressed in the model group; but significantly fell off in the presence of PCs (P < 0.05). Amazingly, all of above indicators showed no significant difference among the groups of different PCs concentrations (P > 0.05). These alterations likewise occurred after TAK-242 pretreatment with or without PCs, ie a notable drop of TLR4, MyD88 and NF-κB appeared in TAK-242 presence, few differences existing when compared to the PCs groups.Conclusion: PCs effectively protect HUVECs from inflammatory and OS damage provoked by HSP serum via blocking TLR4/MyD88/NF-κB signals.Keywords: proanthocyanidins, Henoch-schönlein purpura, TLR4/MyD88/NF-κB, inflammation, oxidative stress
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