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Cellular and Molecular Neurobiology

, Volume 27, Issue 7, pp 909–921 | Cite as

Induction of TNF-α by LPS in Schwann Cell is Regulated by MAPK Activation Signals

  • Chun Cheng
  • Yongwei Qin
  • Xiaoyi Shao
  • Haibo Wang
  • Yongjing Gao
  • Mengling Cheng
  • Aiguo Shen
Original Paper

Abstract

Mitogen-activated protein kinases (MAPKs) are important mediators of cytokine expression and are critically involved in the immune response. The lipopolysaccharide (LPS) of gram-negative bacteria induces the expression of cytokines and proinflammatory genes via the toll-like receptor 4 (TLR4) signaling pathway in diverse cell types. In vivo, Schwann cells (SCs) at the site of injury may also produce tumor necrosis factor-- α (TNF-α). However, the precise mechanisms of TNF-α synthesis are still not clear. The purpose of the present study was to elucidate the underlying molecular mechanisms in the cultured SCs for its ability to activate the MAPKs and TNF-α gene, in response to LPS. Using enzyme-linked immunosorbent assay (ELISA), it was confirmed that treatment with LPS stimulated the synthesis of TNF-α in a concentration- and time-dependent manner. Intracellular location of TNF-α was detected under confocal microscope. Moreover, LPS activated extracellular signal-regulated kinase (ERK1/2), P38 and stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and induced their phosphorylation. LPS-elicited SCs TNF-α production was also drastically suppressed by PD98059 (ERK inhibitor), SB202190 (P38 inhibitor), or SP600125 (SAPK/JNK inhibitor). Additionally, the expression of CD14 and TLR4 was examined by RT–PCR. It was demonstrated that the expression of CD14, TLR4 was crucial for the SCs responses to LPS. In conclusion, the results provide novel mechanisms for the response of SCs to LPS stimulation, through MAPKs signaling pathways.

Keywords

Lipopolysaccharide Schwann cell Tumor necrosis factor-alpha Mitogen-activated protein kinase 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (NSFC); grant numbers: 30300099, 30500153, 30770488.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Chun Cheng
    • 1
    • 2
  • Yongwei Qin
    • 3
  • Xiaoyi Shao
    • 2
  • Haibo Wang
    • 2
  • Yongjing Gao
    • 4
  • Mengling Cheng
    • 2
  • Aiguo Shen
    • 1
  1. 1.Key Laboratory for Neuroregeneration of JiangSu ProvinceNantong UniversityNantongPR China
  2. 2.Department of Microbiology and Immunology, Medical CollegeNantong UniversityNantongPR China
  3. 3.Department of Parasitology, Medical CollegeNantong UniversityNantongPR China
  4. 4.Institute of Nautical MedicineNantong UniversityNantongPR China

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