[Influence of signal transduction modulators on the secretory function of T lymphocytes in severely scalded mice and its mechanism].
OBJECTIVE
To investigate the influence of various signal transduction modulators on the splenic T lymphocytes secretion of IL-2 and IL-10 in severely scalded mice, and to explore its mechanism.


METHODS
The mice were inflicted with 18% TBSA full-thickness scald by high-pressure heat vapour, and T lymphocytes were isolated from murine splenocytes through nylon wool column at 12 and 96 post-scald hours (PSH). Then the cells were divided into following groups: i. e. control, scald, scald and modulator [1 ml of 50 micromol/L PKC inhibitor ( H-7) , 30 micromol/L tetradecanoylphorbol-13-acetate (TPA) , 10micromol/L nonreceptor tyrosine protein kinase inhibitor (herbimycin) , 25 microg/ml of mitogen activated protein kinase kinase inhibitor (PD098059) , 100 nmol/L Calcium ionophore ( A23187) were added to the cells, respectively] groups. The scald group was subdivided into S1 (with scald at 12 PSH) and S2 (with scald at 96 PSH) groups. The modulator group was subdivided into modulator, S1 and modulator( the modulators were added into cells at 12 PSH) , and S2 and modulator( the modulators were added to cells at 96 PSH) groups. The influence of modulators to T lymphocyte secretion of IL-2 and IL-10 were observed.


RESULTS
After the addition of H-7, the IL-2 and IL-10 levels in each group were obviously lower than that in controls( P <0. 05 or 0.01) , and that in S1 and H7 group, S2 and H7 group were obviously lower than that in scald group at corresponding time-points( P <0.01). The levels of IL-10, and especially IL-2 were elevated by TPA, but they were markedly lower than that in control group after PD098059 pretreatment. The secretion of IL-2 and IL-10 was significantly suppressed by herbimycin in S1 and herbimycin, and S2 and herbimycin groups, but those in Sl and A21387[ (2 417+/-39) pg/ml, (2 793+/-25)pg/ml] , S2 and A21387 [ (921+/-50) pg/ml, (2 633+/-35)pg/ml] groups were evidently higher than those in S1[ (1 542+/-40)pg/ml, (2 390+/-15)pg/ml] , S2 [(328+/-19)pg/ml, (1 618+/-21)pg/ml,( P <0.05 or <0.01)]groups.


CONCLUSIONS
PKC, calcium, MAPKK and TPK play critical roles in the dysfunction of splenic T lymphocyte secretion of IL-2 and IL-10 in severely scalded mice, among which TPK and PKC are mainly targeted to IL-2 secretion, and MAPKK is targeted to IL-10 secretion. TPA and A23187 can markedly rectify the disturbance of IL-2/IL-10 secretion ratio by increasing the IL-2 secretion after scald.
Zheng
Jun-song
JS
Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combine Injury, the Third Military Medical University, Chongqing, PR China.
Peng
Dai-zhi
DZ
Huang
Wen-hua
WH
Luo
Gao-xing
GX
Huang
Hui
H
Liu
Jing
J
Zhou
Xin
X
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D002056:Burns / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016227:Benzoquinones; D005419:Flavonoids; D007376:Interleukin-2; D047029:Lactams, Macrocyclic; D016753:Interleukin-10; D017828:Rifabutin; D000001:Calcimycin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D020929:Mitogen-Activated Protein Kinase Kinases; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium