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Prostaglandin I 2 analogs inhibit Th1 and Th2 effector cytokine production by CD4 T cells
Author(s) -
Zhou Weisong,
Blackwell Timothy S.,
Goleniewska Kasia,
O’Neal Jamye F.,
FitzGerald Garret A.,
Lucitt Margaret,
Breyer Richard M.,
Peebles R. Stokes
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0606375
Subject(s) - biology , cytokine , microbiology and biotechnology , receptor , cd28 , effector , immune system , t cell , signal transduction , immunology , biochemistry
An anti‐inflammatory effect of PGI 2 has been suggested by increased inflammation in mice that are deficient in the PGI 2 receptor (IP) or in respiratory syncytial viral‐ or OVA‐induced CD4 T cell‐associated responses. To determine the mechanism of the anti‐inflammatory effect, we hypothesized that PGI 2 analogs inhibit CD4 T cell effector cytokine production. To test this hypothesis, we activated purified CD4 T cells with anti‐CD3 and anti‐CD28 antibodies under Th1 and Th2 polarizing conditions for 4 days and restimulated the T cells with anti‐CD3 in the presence of PGI 2 analogs for 2 days. We found that PGI 2 analogs (cicaprost and iloprost) inhibited the production of Th1 cytokines (IFN‐γ) and Th2 cytokines (IL‐4, IL‐10, and IL‐13) in a dose‐dependent pattern. The inhibitory effect was partially dependent on the IP receptor signaling and was correlated with elevated intracellular cAMP and down‐regulated NF‐κB activity. Pretreatment of the CD4 T cells with 8‐bromoadenosine‐3′,5′‐cyclic monophosphorothioate, Rp‐isomer, to inhibit a key signaling molecule in the cAMP pathway, protein kinase A (PKA), attenuated the suppressive effect of PGI 2 analogs significantly, suggesting that PKA, in part, mediates the inhibition of the cytokine production. These data indicate that PGI 2 analogs have an immune‐suppressive effect on previously activated and differentiated CD4 T cells in vitro and suggest that PGI 2 may have a similar function in vivo.