Induction of tumor necrosis-alpha, p38 and JNK in the spinal cord following acute heart injury in the rat model.
BACKGROUND
It is still not known whether the spinal cytokine signaling pathways are involved in the pathophysiologic mechanism of the acute phase of heart disease. This study examines the expression pattern of tumor necrosis factor-alpha (TNF-alpha) and its two related mitogenic-activated protein kinases, p38 and Jun-N-terminal kinase (JNK), in the spinal cord in response to acute cardiac injury (ACI).


METHODS
The ACI rat model was established by intra-myocardial injection of formalin. At the indicated times after the establishment of ACI, the thoracic segments of the spinal cord were harvested and Western blot was performed to determine the expression of TNF-alpha, p38 and JNK. The localization of the cytokine and the kinases was determined by immunohistochemistry and double immunofluorescence.


RESULTS
In response to ACI, TNF-alpha protein was up-regulated and reached a peak level at 6 h after ACI. The up-regulated TNF-alpha was distributed in all the laminae in the spinal cord and mainly localized in the neurons, as determined by immunohistochemistry and double immunofluorescence. In response to ACI, p38 and JNK were also up-regulated in the spinal cord. The expression profiles of p38 and JNK were similar to that of activated TNF-alpha following ACI.


CONCLUSIONS
This study shows that cardiac injury can induce the activation of spinal TNF-alpha, p38 and JNK. The activated spinal cytokine signaling may contribute to disease progression in the acute phase of cardiac injury in clinical practice.
Dai
R-P
RP
Department of Anesthesia, Second Xiang-Ya Hospital, Central South University, Changsha, China. jmxu001@yahoo.com.cn
Xu
J-M
JM
Tao
L-J
LJ
Li
L
L
Li
Z-P
ZP
Zhang
J-Y
JY
D000818:Animals; D005404:Fixatives; D005557:Formaldehyde; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D009203:Myocardial Infarction / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D005404:Fixatives; D014409:Tumor Necrosis Factor-alpha; D005557:Formaldehyde; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases