JAK2/STAT3 pathway mediating inflammatory responses in heatstroke-induced rats.
Heatstroke not only directly induces cell injury, but also causes large amounts of inflammatory mediators release and cells with extensive biological activities to induce a systemic inflammatory response and immune dysfunction. This study aimed to observe the effects of JAK2 inhibitor AG490 on the brain injury and inflammatory responses of rats with systemic heatstroke. Under the light microscope, the hippocampus tissues of rat with heatstroke were edema and apoptotic rate was increased. Up-regulation of malondialdehyde (MDA), nitric oxide synthase (iNOS), reactive oxygen species (ROS) and down-regulation of superoxide dismutase (SOD) were also found after heatstroke in rats, which compared with that of the control group. Heatstroke induced inflammation factors secretions and up-regulated levels of matrix metallopeptidase 2 and 9 (MMP2 and MMP-9) and systemic inflammatory response molecules including intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-beta 1 (TNF-β1) and cyclooxygenase-2 (COX-2). However, the JAK2 inhibitor AG490 was significantly attenuated the brain injury and inflammatory responses induced by heatstroke in rats. The survival time of heatstroke rats showed that AG490 notably lived longer than heatstroke rats without AG490 treatment. These findings suggest that AG490 may prevent the occurrence of heatstroke via inhibiting the JAK2/STAT3 pathway and the systemic inflammatory responses.
Department of Neurology, General Hospital of Jinan Military Command Jinan 250031, Shandong, China.
Zhen
Z
Tao
Department of Neurology, General Hospital of Jinan Military Command Jinan 250031, Shandong, China.
Ming
M
Cheng
Department of Neurology, General Hospital of Jinan Military Command Jinan 250031, Shandong, China.
Shu-Cai
SC
Wang
Department of Neurology, General Hospital of Jinan Military Command Jinan 250031, Shandong, China.
Wei
W
Lv
Department of Neurology, General Hospital of Jinan Military Command Jinan 250031, Shandong, China.
Huai-Qiang
HQ
Hu
Department of Neurology, General Hospital of Jinan Military Command Jinan 250031, Shandong, China.
Chuan-Fen
CF
Li
Department of Neurology, General Hospital of Jinan Military Command Jinan 250031, Shandong, China.
Bing-Zhen
BZ
Cao
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001929:Brain Edema / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051546:Cyclooxygenase 2 / Q000378:metabolism; D018883:Heat Stroke / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D013482:Superoxide Dismutase; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
AG490; Heatstroke; JAK2/STAT3; inflammation