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
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  • Published online on: June 10, 2013     https://doi.org/10.3892/etm.2013.1152
  • Pages: 459-464
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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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August 2013
Volume 6 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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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