[The role of p38 mitogen-activated protein kinase in interleukin-6 induction by lipopolysaccharide in vascular smooth muscle cells].
OBJECTIVE
To investigate the regulation mechanism of p38 mitogen-activated protein kinase (p38MAPK) in interleukin-6 (IL-6) expression of vascular smooth muscle cell (VSMC) induced by lipopolysaccharide (LPS).


METHODS
Rat VSMCs were divided into LPS group, SB203580+LPS group, SB203580 group and control group. LPS group was treated with 100 microg/L LPS for 0, 3, 6, 12, 24 hours, SB203580+LPS group was first treated with 10 micromol/L SB203580 for 2 hours and then exposed to 100 microg/L LPS for 0, 3, 6, 12, 24 hours, SB203580 group was pretreated with 10 micromol/L SB203580 for 2 hours. The level of IL-6 mRNA was determined by real-time polymerase chain reaction (PCR) and IL-6 secretion in the culture medium was measured by enzyme linked immunosorbent assay (ELISA) at different time points.


RESULTS
The expression of IL-6 mRNA and the release of IL-6 were increased significantly in VSMC as early as 3 hours after being treated with LPS [mRNA: (21.3+/-3.2)x10(4), protein: (296.2+/-19.6) ng/L], peaked in 12 hours [mRNA: (131.4+/-11.2)x10(4), protein: (897.7+/-34.0) ng/L], and the elevation persisted up to 24 hours after treatment [mRNA: (15.3+/-4.7)x10(4), protein: (194.3+/-24.0) ng/L] compared with control group [mRNA: (9.4+/-1.9)x10(4), protein: (29.4+/-4.4) ng/L, all P<0.05]. On the other hand, the expression of IL-6 was significantly suppressed by p38MAPK inhibitor SB203580 at 3, 6, 12 hours [mRNA: (15.4+/-3.6)x10(4), (43.2+/-6.6)x10(4), (56.2+/-5.5)x10(4), protein: (180.3+/-23.6), (432.2+/-56.8), (546.2+/-57.9) ng/L, all P<0.05].


CONCLUSIONS
The release of IL-6 and the expression of IL-6 mRNA was increased significantly in LPS-challenged VSMC; however, the induction of IL-6 was significantly suppressed by p38MAPK inhibitor. p38MAPK may play an important role in the release of IL-6 induced by LPS.
Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China.
Yu-feng
YF
Chu
Yi
Y
Jiang
Ji-cheng
JC
Zhang
Hong-sheng
HS
Ren
Jin-jiao
JJ
Jiang
Mei
M
Meng
Chun-ting
CT
Wang
D000818:Animals; D002478:Cells, Cultured; D007093:Imidazoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*
D007093:Imidazoles; D015850:Interleukin-6; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580