Ghrelin is involved in regulating the progression of Echinococcus Granulosus-infected liver lesions through suppression of immunoinflammation and fibrosis.

Autor: Zhu, Jiang, Zhao, Hongqiong, Aierken, Aili, Zhou, Tanfang, Menggen, Meng, Gao, Huijing, He, Rongdong, Aimulajiang, Kalibixiati, Wen, Hao
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Zdroj: PLoS Neglected Tropical Diseases; 10/22/2024, Vol. 18 Issue 10, p1-23, 23p
Abstrakt: Background: Cystic Echinococcosis (CE) is a zoonotic disease causing fibrosis and necrosis of diseased livers caused by infection with Echinococcus granulosus (E.g). There is evidence that E.g is susceptible to immune escape and tolerance when host expression of immunoinflammation and fibrosis is suppressed, accelerating the progression of CE. Ghrelin has the effect of suppressing immunoinflammation and fibrosis, and whether it is involved in regulating the progression of E.g-infected liver lesions is not clear. Methods: Serum and hepatic Ghrelin levels were observed in E.g-infected mice (4, 12 and 36 weeks) and compared with healthy control groups. Co-localization analysis is performed between protein expression of Ghrelin in and around the hepatic lesions of E.g-infected 12-week mice and protein expression of different hepatic histiocytes by mIHC. HepG2 cells and protoscoleces (PSCs) protein were co-cultured in vitro, as well as PSCs were alone in vitro, followed by exogenously administered of Ghrelin and its receptor blocker, [D-Lys3]-GHRP-6, to assess their regulatory effects on immunoinflammation, fibrosis and survival rate of PSCs. Results: Serum Ghrelin levels were increased in E.g-infected 4- and 12-week mice, and reduced in 36-week mice. E.g-infected mice consistently recruited Ghrelin in and around the hepatic lesions, which was extremely strongly co-localized with the protein expression of hepatic stellate cells (HSCs), T cells and the TGF-β1/Smad3 pathway. The secretion of Ghrelin was increased with increasing concentrations of PSCs protein in HepG2 cells culture medium. Moreover, Ghrelin could significantly inhibit the secretion of IL-2, INF-γ and TNF-α, as well as the expression of Myd88/NF-κB and TGF-β1/Smad3 pathway protein, and promoted the secretion of IL-4 and IL-10. Blocking Ghrelin receptor could significantly inhibit PSCs growth in in vitro experiment. Conclusion: Ghrelin is highly expressed in the early stages of hepatic E.g infection and may be involved in regulating the progression of liver lesions by suppression immunoinflammation and fibrosis. Author summary: There is evidence that Echinococcus granulosus (E.g) is susceptible to immune escape and tolerance when host expression of immunoinflammation and fibrosis is suppressed, accelerating the progression of hepatic cystic Echinococcosis (CE). Ghrelin has the effect of suppressing immunoinflammation and fibrosis, and whether it is involved in the regulation of CE progression is not clear. The present study demonstrated that Ghrelin is highly expressed in the early stage of hepatic E.g infection and may act mainly on hepatic stellate cells and T cells, exerting biological effects to inhibit Th1-type cellular immunity, the Myd88/NF-κB and TGF-β1/Smad3 pathways and agonize Th2-type cellular immunity, which in turn suppresses host expression of immunoinflammation and fibrosis. However, this biological effect of Ghrelin may regulate the progression of CE. [D-Lys3]-GHRP-6, as a Ghrelin receptor blocker, is expected to be a drug target against CE. In addition, we found protoscoleces of E.g with gene expression of Ghrelin, which also provides some evidence that Ghrelin regulates the disease progression of CE. Our study reveals the possible regulatory role and mechanism of Ghrelin in the process of hepatic E.g infection. In-depth studies could help to further unravel the disease mechanisms of CE and provide potential targets for therapy. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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