[Effect of Interleukin-17 on neutrophil apoptosis].
OBJECTIVE
To study the effect of Interleukin(IL)-17 on neutrophil apoptosis and try to explain the possible mechanism involved.


METHODS
Neutrophils isolated from healthy donors were incubated in enriched RPMI 1640 cell culture medium at 37 degrees C in 5% carbon dioxide. Subgroups were incubated with IL-17, heat-denatured IL-17 (X-IL-17), dexamethasone (DEX), or buffer alone. Apoptosis was assessed by morphologic changes, by detecting DNA strand breaks. Production of proapoptotic protein Bax by neutrophils was evaluated by immunocytochemistry.


RESULTS
At the time of neutrophil incubation, neutrophils in the control subsets exhibited morphologic evidence of apoptosis. A steady rise in apoptosis index (AI) was noted, with (1.54+/-0.08)% for 0 h, (11.48+/-1.80)% (compared with 0 h, P<0.05) for 12 h and (34.19+/-1.92)% (compared with 0 h, P<0.01) for 24 h, respectively. IL-17 at concentration of 50 microg/L resulted in increased AI of neutrophils, with (1.43+/-0.17)% (compared with control 0 h, P>0.05) for 0 h, (20.47+/-6.22)% (compared with control 12 h, P<0.01) for 12 h and (40.74+/-3.48)% (compared with control 24 h, P<0.05) for 24 h, respectively. While at concentrations of 5 mug/L and 0.5 microg/L, IL-17 resulted in decreased AI, with (14.24+/-4.26)% (compared with control 24 h, P<0.01) for 24 h, and (19.86+/-4.39)% (compared with control 24 h, P<0.01) for 24 h, respectively. AI of neutrophils treated with X-IL-17 at concentration of 50 ng/ml for 24 h was (33.22+/-1.61)% (compared with control 24 h, P>0.05). Neutrophils apoptosis was accompanied by DNA fragmentation. In all groups, the increasing of Bax immunoreactivity was strongly related with more apoptotic neutrophils (r=0.932, P<0.01).


CONCLUSIONS
In vitro, IL-17 modulates apoptosis of neutrophils. At higher concentrations, it accelerates neutrophils apoptosis. At lower concentrations, it delays neutrophils apoptosis. Modulation of the expression of Bax by IL-17 may be one of the possible inner mechanisms.
Zhang
Zhi-gang
ZG
Department of Geriatric Medicine, Peking University First Hospital, Beijing 100034, China.
He
Quan-ying
QY
Liu
Xin-min
XM
Tang
Xiu-ying
XY
Chen
Lu-zeng
LZ
D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
D020381:Interleukin-17; D051028:bcl-2-Associated X Protein; D003907:Dexamethasone