Journal of Infection
Volume 61, Issue 2 , Pages 173-184, August 2010

Amphotericin B regulates the host immune response in visceral leishmaniasis: Reciprocal regulation of protein kinase C isoforms

  • Asok Kumar Mukherjee

      Affiliations

    • Div. of Molecular Medicine, Bose Institute, Kolkata, India
    • Employees State Insurance Hospital, Maniktala, Kolkata, India
  • ,
  • Gaurav Gupta

      Affiliations

    • Div. of Molecular Medicine, Bose Institute, Kolkata, India
  • ,
  • Surajit Bhattacharjee

      Affiliations

    • Div. of Molecular Medicine, Bose Institute, Kolkata, India
  • ,
  • Subhasis Kamal Guha

      Affiliations

    • School of Tropical Medicine, Kolkata, India
  • ,
  • Saikat Majumder

      Affiliations

    • Div. of Molecular Medicine, Bose Institute, Kolkata, India
  • ,
  • Anupam Adhikari

      Affiliations

    • Div. of Molecular Medicine, Bose Institute, Kolkata, India
  • ,
  • Parna Bhattachrya

      Affiliations

    • Div. of Molecular Medicine, Bose Institute, Kolkata, India
  • ,
  • Suchandra Bhattacharyya Majumdar

      Affiliations

    • Div. of Molecular Medicine, Bose Institute, Kolkata, India
  • ,
  • Subrata Majumdar

      Affiliations

    • Div. of Molecular Medicine, Bose Institute, Kolkata, India
    • Corresponding Author InformationCorresponding author at: Div. of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700054, India. Tel.: +91 2337 9416/9544/9219; fax: +91 (33) 2334 3886.

Accepted 13 May 2010. published online 11 June 2010.

Summary 

Objectives

Treatment of visceral leishmaniasis (VL) is marked by the failure of pentavalent antimonials which has brought amphotericin B (AmpB) to the forefront. In this study we have focused on signaling pathway regulating AmpB triggered effector response.

Methods

AmpB triggered effector response in the form of free radicals and proinflammatory cytokines was determined by FACS, colorimetric estimation or Real-Time PCR (RT-PCR). Specific peptide inhibitors for classical and atypical protein kinase C (PKC) were used to investigate the role of PKC isoforms in the functioning of AmpB during VL.

Results

In vitro studies with THP1 cells showed that 2 μg/ml dose of AmpB could mediate effective parasite clearance due to strong induction of free radicals and proinflammatory cytokines. This induction of proinflammatory response paralleled with antagonistic regulation of classical and atypical PKC. Further confirmation was provided by RT-PCR of (peripheral blood mononuclear cells) PBMC isolated from VL infected patients undergoing AmpB treatment.

Conclusions

Overall, our results suggest that classical and atypical PKC signaling pathways are involved in the modulation of proinflammatory response triggered by AmpB against Leishmania donovani. These observations may contribute to the understanding of the mechanism responsible for the initiation of protective response induced by AmpB during VL.

Keywords: Amphotericin B, Visceral leishmaniasis, Protein kinase C, THP1

To access this article, please choose from the options below

Login to an existing account or Register a new account.

  • Purchase this article for 31.50 USD (You must login/register to purchase this article)

    Online access for 24 hours. The PDF version can be downloaded as your permanent record.

  • Subscribe to this title

    Get unlimited online access to this article and all other articles in this title 24/7 for one year.

  • Claim access now

    For current subscribers with Society Membership or Account Number.

  • Visit SciVerse ScienceDirect to see if you have access via your institution.
 

PII: S0163-4453(10)00149-0

doi:10.1016/j.jinf.2010.05.003

Journal of Infection
Volume 61, Issue 2 , Pages 173-184, August 2010