Neurotoxicity Research

, Volume 34, Issue 1, pp 137–146 | Cite as

Upregulation of Pro-inflammatory Cytokine Expression Following Chronic Paracetamol Treatment in Astrocyte

  • Nutnicha Tantarungsee
  • Waranurin Yisarakun
  • Thananya Thongtan
  • Laddawan Lalert
  • Sirinapa Srikam
  • Preecha Reuangwechvorachai
  • Praewphan Ingruanglert
  • Supang Maneesri-le Grand


The present study aimed to investigate the effect of APAP treatment on the expression of pro-inflammatory cytokines in the astrocytes. The mouse astrocyte cells (C8-D1A) were treated with APAP at the concentration of 100 μM for 24 h, 16 and 28 days. The expressions of pro-inflammatory cytokines and NF-kB were determined using western blot analysis. Furthermore, the expression and localization of phosphorylation of NF-kB were detected by immunohistochemical and immunofluorescent analysis. The ultrastructure of C8-D1A cells was as well monitored. The results revealed that acute APAP treatment (24 h) had no effect on the expression of pro-inflammatory cytokines and pNF-kB. This treatment did not alter the ultrastructure of C8-D1A cells when compared with those in the control cells. However, the results obtained from the study on chronic APAP-treated cells (16 and 28 days) showed the different effect of APAP treatment. The results obtained from western blot analysis showed the increment of pro-inflammatory cytokine (IL-1β and TNF-α) expressions and the activation of NF-kB signaling pathway. Nuclear translocation of pNF-kB and alteration of several cell structures were well observed in the C8-D1A cells with chronic APAP treatment. The results obtained from this study suggest that chronic APAP treatment can induce an upregulation of pro-inflammatory cytokines (IL-1β and TNFα) in astrocytes. This alteration implies the involvement of the activation of NF-kB signaling pathway.


Paracetamol Astrocyte Pro-inflammatory cytokines NF-kB signaling Ultrastructure 



This study was supported by the National Research Council of Thailand (NRCT, GB_B_60_071_30_15 and GB_B_60_074_30_18)


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Nutnicha Tantarungsee
    • 1
  • Waranurin Yisarakun
    • 2
  • Thananya Thongtan
    • 3
  • Laddawan Lalert
    • 1
  • Sirinapa Srikam
    • 1
  • Preecha Reuangwechvorachai
    • 1
  • Praewphan Ingruanglert
    • 4
  • Supang Maneesri-le Grand
    • 1
  1. 1.Department of Pathology, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  2. 2.Department of Biomedical Sciences, Faculty of Allied Health SciencesBurapha UniversityChonBuriThailand
  3. 3.Department of Biochemistry, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  4. 4.Stem Cells and Cell Therapy Research Unit, Faculty of MedicineChulalongkorn UniversityBangkokThailand

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