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T-kininogen, a cystatin-like molecule, inhibits ERK-dependent lymphocyte proliferation
Ist Teil von
Mechanisms of ageing and development, 2005-12, Vol.126 (12), p.1284-1291
Ort / Verlag
Shannon: Elsevier Ireland Ltd
Erscheinungsjahr
2005
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Plasma levels of kininogens increase with age in both rats and humans. Kininogens are inhibitors of cysteine proteinases, and filarial cysteine proteinase inhibitors (cystatins) reduce the proliferation of T cells. We evaluated whether T-kininogen (T-KG) might mimic this effect, and here we present data indicating that exposure of either rat splenocytes or Jurkat cells to purified T-KG results in inhibition of both ERK activation and [
3H]-thymidine incorporation, both basal and in response to ConA or PHA. Interestingly, T-KG did not impair [
3H]-thymidine incorporation in response to IL-2, which requires primarily the activation of the JNK and Jak/STAT pathways. These effects were neither the consequence of increased cell death, nor required the activity of kinin receptors. Furthermore, when T cell receptor proximal events were bypassed by the use of PMA plus Calcium ionophore, T-KG no longer inhibited ERK activation, suggesting that inhibition occurs upstream of these events, possibly at the level of membrane associated signal transduction molecules. We conclude that, like filarial cystatins, T-KG inhibits ERK-dependent T cell proliferation, and these observations suggest a possible role for T-KG in immunosenescence.