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Nicotine regulates FasL, activates Mst‐1, promotes Histone H2B phosphorylation and accelerates neutrophil apoptosis
Author(s) -
Rane Madhavi Jagdish,
Kumar Jay,
Jin Shunying,
Merchant Michael,
Ritzenthaler Jeffery,
Roman Jesse,
Klein Jon
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb109
Subject(s) - fas ligand , p38 mitogen activated protein kinases , apoptosis , nicotine , chemistry , microbiology and biotechnology , mapk/erk pathway , phosphorylation , cancer research , biology , medicine , biochemistry , programmed cell death
An efficient way of resolving inflammation is induction of neutrophil apoptosis. We hypothesized that nicotine accelerates neutrophil apoptosis. Nicotine (3 mM) accelerated human neutrophil apoptosis by enhancing caspase‐3 cleavage in a p38 and ERK dependent manner. LPS‐induced neutrophil survival was significantly inhibited by nicotine. Moreover, □4nAChR antagonist Dihydro‐β‐erythroidine hydrobromide (D□E), inhibited nicotine‐stimulated pERK, pP38 and caspase‐3 cleavage. Caspase‐3 cleavage promoted Mst‐1 cleavage and pSer14‐Histone H2B which correlates with apoptotic chromatin and onset of apoptosis. Mst‐1 cleavage and pSer14‐Histone H2B were dependent upon p38 and ERK. In addition, nicotine induced FasL expression and secretion in neutrophils. Blockade of □4 AChR, p38 and ERK pathways inhibited nicotine‐induced FasL expression. Furthermore, blockade of FasL with anti‐FasL antibody prevented nicotine‐induced caspase‐3 cleavage and neutrophil apoptosis. These results suggest that nicotine stimulates an extrinsic apoptotic cascade in human neutrophils. Thus, FasL/Fas system in neutrophils could serve as a target for further investigation of the cholinergic system in neuroimmunomodulation. Funding Source: R01AI075212–01 (MJR).