Adenosine-mediated inhibition of cytotoxic activity and cytokine production by IL-2/NKp46-Activated NK cells
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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 WordsNK cells PKA Adenosine Cytotoxicity Cytokines
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- 21.Staples KJ, Bergmann M, Tomita K, et al: Adenosine 3′,5′-cyclic monophosphate (cAMP)-dependent inhibition of IL-5 from human T lymphocytes is not mediated by the cAMP-dependent protein kinase A. Immunol 2001;167:2074–2080.Google Scholar