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Immunologic Research

, Volume 36, Issue 1–3, pp 91–99 | Cite as

Adenosine-mediated inhibition of cytotoxic activity and cytokine production by IL-2/NKp46-Activated NK cells

Involvement of Protein kinase a isozyme I (PKAI)
  • Tatiana Raskovalova
  • Anna Lokshin
  • Xiaojun Huang
  • Edwin K. Jackson
  • Elieser Gorelik
Article

Abstract

Adenosine suppresses the production of various cytokines/ chemokines and inhibits the cytotoxic activity of murine and human NK cells activated with IL-2 or Ly49D, NKp46-receptor crosslinking, respectively. These effects are mediated by the type A2A adenosine receptor via stimulation of adenylyl cyclase, increased production of cAMP, and activation of PKA. PKA I, but not PKA II, participates in the inhibitory effects of adenosine. Blocking regulatory, but not catalytic, subunits of PKA I abrogates the inhibitory effects of adenosine. These findings suggest that tumor-produced adenosine inhibits the activity of NK and other effector cells and thereby protects tumors from immune-mediated destruction.

Key Words

NK cells PKA Adenosine Cytotoxicity Cytokines 

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Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Tatiana Raskovalova
    • 1
  • Anna Lokshin
    • 4
  • Xiaojun Huang
    • 1
  • Edwin K. Jackson
    • 3
    • 4
  • Elieser Gorelik
    • 1
    • 2
  1. 1.Department of PathologyUniversity of Pittsburgh University of Pittsburgh Cancer InstitutePittsburgh
  2. 2.Department of ImmunologyUniversity of Pittsburgh, University of Pittsburgh Cancer InstitutePittsburgh
  3. 3.Department PharmacologyUniversity of Pittsburgh, University of Pittsburgh Cancer InstitutePittsburgh
  4. 4.Department Medicine and Center for Clinical PharmacologyUniversity of Pittsburgh, University of Pittsburgh Cancer InstitutePittsburgh

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