Age-related impairment of GM-CSF-induced signalling in neutrophils: role of SHP-1 and SOCS proteins.

Abstract:

:Functional activities of mature human neutrophils are strongly influenced by the pro-inflammatory cytokine granulocyte macrophage-colony stimulating factor (GM-CSF). Accordingly, a defective response to GM-CSF might have dramatic consequences for neutrophil functions and the host defence against infections. Such an event is most likely to occur in senescence. A number of studies have, in fact, reported an impairment of the GM-CSF capacity to prime and/or to activate respiratory burst, as well as to delay apoptotic events, in neutrophils from elderly individuals. In the last 2 decades many efforts have been made to explore at molecular levels the mechanism underlying these defects. Recent studies let us depict a scenario in which an increased activity of inhibitory molecules, such as Src homology domain-containing protein tyrosine phosphatase-1 (SHP-1) and suppressors of cytokine signalling (SOCS), is responsible for the age-related failure of GM-CSF to stimulate neutrophil functions via inhibition of Lyn-, phosphoinositide 3-kinase (PI3-K)/extracellular signal-regulated kinase (ERK)- and signal transducers and activators of transcription (STAT)-dependent pathways. The control of SHP-1 and/or SOCS activity might therefore be an important therapeutic target for the restoration of normal immune responses during senescence.

journal_name

Ageing Res Rev

journal_title

Ageing research reviews

authors

Tortorella C,Simone O,Piazzolla G,Stella I,Antonaci S

doi

10.1016/j.arr.2006.10.001

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

81-93

issue

2

eissn

1568-1637

issn

1872-9649

pii

S1568-1637(06)00081-X

journal_volume

6

pub_type

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