Substance-P prevents the cholestatic liver injury by regulating inflammatory responses.

Publisher: Elsevier Science Inc Country of Publication: United States NLM ID: 8008690 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-5169 (Electronic) Linking ISSN: 01969781 NLM ISO Abbreviation: Peptides Subsets: MEDLINE

Publication: New York, NY : Elsevier Science Inc.
Original Publication: Fayetteville, N. Y., Ankho International.

Cholestasis/*drug therapy ; Inflammation/*drug therapy ; Liver/*drug effects ; Liver Cirrhosis/*drug therapy ; Substance P/*pharmacology; Animals ; Apoptosis/drug effects ; Cholestasis/blood ; Cholestasis/immunology ; Cholestasis/pathology ; Common Bile Duct/drug effects ; Common Bile Duct/pathology ; Common Bile Duct/surgery ; Gene Expression Regulation/immunology ; Humans ; Inflammation/blood ; Inflammation/immunology ; Inflammation/pathology ; Interleukin-10/blood ; Ligation/adverse effects ; Liver/immunology ; Liver/injuries ; Liver Cirrhosis/blood ; Liver Cirrhosis/genetics ; Liver Cirrhosis/pathology ; Matrix Metalloproteinase 9/blood ; Rats ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Transforming Growth Factor beta1/blood ; Tumor Necrosis Factor-alpha/blood

Substance-P (SP) is a neuropeptide that modulates immune responses and accelerates tissue repair in critical inflammatory disease. Liver fibrosis and cirrhosis are the ultimate outcomes of almost all chronic liver diseases caused by viral infection, steatohepatitis, autoimmune, and cholestatic injury. Despite the development of new drugs, liver transplantation is still the only fundamental treatment; thus, new therapeutic approaches to mitigate liver fibrosis and chronic inflammation are constantly being needed. The aim of this study was to examine the effect of SP on liver damage due to cholestatic stress. To induce cholestatic injury, common bile duct ligation (CBDL) was attempted, followed by systemic application of SP. SP treatment increased IL-10 and decreased TNF-α in serum with increasing levels of circulating regulatory T cells (Tregs) from the early stage of CBDL. Moreover, SP decreased CBDL-induced TGF-β1 expression in the circulation. This could create anti-inflammatory/anti-fibrotic environment under CBDL, which might ameliorate the progression of liver fibrosis in CBDL. Histological and molecular analysis revealed that SP treatment reduced ductular reaction, hepatic damage, and apoptotic hepatocytes, accompanied by diminishing type I collagen and upregulating MMP-9. These studies found that SP is a promising therapeutic candidate for immune-related liver disease as well as cholestatic liver disease, by providing hepatic protective effects via immune suppression.
(Copyright © 2021 Elsevier Inc. All rights reserved.)

Keywords: Cholestatic liver disease; Fibrosis; Immune suppression; Regulatory T cell; Substance-P

0 (TGFB1 protein, human)
0 (Transforming Growth Factor beta1)
0 (Tumor Necrosis Factor-alpha)
130068-27-8 (Interleukin-10)
33507-63-0 (Substance P)
EC 3.4.24.35 (Matrix Metalloproteinase 9)

Date Created: 20210113 Date Completed: 20211227 Latest Revision: 20211227

20231215

10.1016/j.peptides.2021.170494

33440226