Activation and clinical significance of p38 MAPK signaling pathway in patients with severe trauma.
BACKGROUND
Organ dysfunction or multiple organ dysfunction syndrome caused by developing immunological dysfunction and subsequent sepsis or the systemic inflammatory response syndrome after trauma is the leading cause of death in trauma patient. It is believed that mitogen-activated protein kinase) (p38MAPK) is one of the most important kinases in inflammatory signaling. In this study, the change of p38 MAPK signaling pathway in trauma patient with different severity and its clinical significance in trauma inflammation were investigated.


METHODS
One hundred fifty major trauma patients were included in the study and divided into three groups according to injury severity score (ISS). All data required to calculate ISS and determine organ function were registered on admission and during the ICU-stay. Peripheral blood samples were collected from trauma patients 6 h, 1 d, 3 d, 5 d, and 7 d after injury. RQ-PCR and Western blot was used to examine the changes in gene expression, protein expression, and activation level of leukocyte p38 MAPK. Plasma IL-6 and TNFalpha were assayed by ELISA.


RESULTS
Organ dysfunction in 33 trauma patients developed and eight deaths occurred after 24 h in ICU. The causes of death included severe ARDS, MODS, and irreversible brain injury. Incidence of organ dysfunction was related to the increase of injury severity (P < 0.01). Compared with healthy control, the gene expression of p38 MAPK in trauma patients increased significantly 6 h after injury (P < 0.05), and reached a maximum in 1 d (P < 0.01). The expression maintained a high level for 7 d (P < 0.05). One day after injury, significant elevation was observed in protein expression and activation level of p38 MAPK (P < 0.05), as well as the plasma TNFalpha and IL-6 level (P < 0.01). Further investigation found that the gene expression, protein expression, and activation levels of p38 MAPK increased with higher ISS (P < 0.05), and the elevation of plasma TNFalpha and IL-6 level was associated with the increase of activated p38 MAPK and ISS (P < 0.05).


CONCLUSIONS
p38 MAPK signal pathway was activated in trauma patients. The severity of trauma had highly positive correlation with the expression and activation of p38 MAPK, as well as the elevation of plasma TNFalpha and IL-6 expression. These findings indicate that p38 MAPK signaling pathway plays an important role in the pathological mechanism of trauma.
Wang
Yi Xin
YX
First Aid Center, Shanghai Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Rcipng@hotmail.com
Xu
Xin Yun
XY
Su
Wen Li
WL
Wang
Qiang
Q
Zhu
Wen Xian
WX
Chen
Fen
F
Jin
Ge
G
Liu
Yu Jian
YJ
Li
Yi Dong
YD
Sun
Yan Ping
YP
Gao
Wen Chao
WC
Ruan
Can Ping
CP
D000058:Accidental Falls; D000063:Accidents, Traffic; D000293:Adolescent; D000328:Adult; D000368:Aged; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007962:Leukocytes / Q000201:enzymology; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014951:Wounds, Stab / Q000201:enzymology*; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases