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Article

Substance P participates in immune-mediated hepatic injury induced by concanavalin A in mice and stimulates cytokine synthesis in Kupffer cells

  • Authors:
    • Yan Yang
    • Ming Yan
    • Haitao Zhang
    • Xuping Wang
  • View Affiliations / Copyright

    Affiliations: Health Examination Center, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Interventional Center, Jinan Infectious Disease Hospital, Jinan, Shandong 250021, P.R. China, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
  • Pages: 459-464
    |
    Published online on: June 10, 2013
       https://doi.org/10.3892/etm.2013.1152
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Abstract

Studies have indicated that the immune system plays a pivotal role in hepatitis. Substance P (SP) has been shown to modulate the immune response. In order to investigate the role of SP in liver injury and to determine whether it leads to pro-inflammatory signaling, we established a mouse model of hepatic injury induced by concanavalin A (ConA). We also exposed mouse Kupffer cells (KCs) to SP in vitro. Cytokine and SP levels in liver homogenates were detected using enzyme-linked immunosorbent assay (ELISA) and the protective effects of L-703,606 were evaluated through serological and histological assessments. Neurokinin-1 receptor (NK-1R) expression was evaluated by immunofluorescence and quantitative polymerase chain reaction (PCR). The levels of SP, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly increased in the ConA-treated mice and the levels of ALT and AST were markedly reduced by L-703,606-pretreatment. Liver injury was significantly reduced by treatment with L-703,606. The mouse KCs expressed NK-1R and SP increased NK-1R mRNA expression. Furthermore, NK-1R blockade eliminated the effect of SP on NK-1R mRNA expression. The cytokine levels exhibited a substantial increase in the SP-pretreated KCs compared with the KCs that were cultured in control medium. The interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels in the L-703,606‑pretreated KCs were significantly lower compared with those in the SP-pretreated KCs. Our study suggests that neurogenic inflammation induced by SP plays an important role in hepatitis. Mouse KCs express NK-1R and SP increases NK-1R mRNA expression. SP enhances IL-6 and TNF-α secretion and an NK-1R antagonist inhibits this secretion.
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Copy and paste a formatted citation
Spandidos Publications style
Yang Y, Yan M, Zhang H and Wang X: Substance P participates in immune-mediated hepatic injury induced by concanavalin A in mice and stimulates cytokine synthesis in Kupffer cells. Exp Ther Med 6: 459-464, 2013.
APA
Yang, Y., Yan, M., Zhang, H., & Wang, X. (2013). Substance P participates in immune-mediated hepatic injury induced by concanavalin A in mice and stimulates cytokine synthesis in Kupffer cells. Experimental and Therapeutic Medicine, 6, 459-464. https://doi.org/10.3892/etm.2013.1152
MLA
Yang, Y., Yan, M., Zhang, H., Wang, X."Substance P participates in immune-mediated hepatic injury induced by concanavalin A in mice and stimulates cytokine synthesis in Kupffer cells". Experimental and Therapeutic Medicine 6.2 (2013): 459-464.
Chicago
Yang, Y., Yan, M., Zhang, H., Wang, X."Substance P participates in immune-mediated hepatic injury induced by concanavalin A in mice and stimulates cytokine synthesis in Kupffer cells". Experimental and Therapeutic Medicine 6, no. 2 (2013): 459-464. https://doi.org/10.3892/etm.2013.1152
Copy and paste a formatted citation
x
Spandidos Publications style
Yang Y, Yan M, Zhang H and Wang X: Substance P participates in immune-mediated hepatic injury induced by concanavalin A in mice and stimulates cytokine synthesis in Kupffer cells. Exp Ther Med 6: 459-464, 2013.
APA
Yang, Y., Yan, M., Zhang, H., & Wang, X. (2013). Substance P participates in immune-mediated hepatic injury induced by concanavalin A in mice and stimulates cytokine synthesis in Kupffer cells. Experimental and Therapeutic Medicine, 6, 459-464. https://doi.org/10.3892/etm.2013.1152
MLA
Yang, Y., Yan, M., Zhang, H., Wang, X."Substance P participates in immune-mediated hepatic injury induced by concanavalin A in mice and stimulates cytokine synthesis in Kupffer cells". Experimental and Therapeutic Medicine 6.2 (2013): 459-464.
Chicago
Yang, Y., Yan, M., Zhang, H., Wang, X."Substance P participates in immune-mediated hepatic injury induced by concanavalin A in mice and stimulates cytokine synthesis in Kupffer cells". Experimental and Therapeutic Medicine 6, no. 2 (2013): 459-464. https://doi.org/10.3892/etm.2013.1152
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