Beta-adrenoceptor mediated surgery-induced production of pro-inflammatory cytokines in rat microglia cells.
Immunological changes initiated by major operative injury may result in inflammatory responses in both peripheral and central nervous system, which may lead to organ dysfunction. Recent studies indicate that beta-adrenergic receptors (beta-ARs) may mediate production of pro-inflammatory cytokines in the brain. In the present study propranolol (beta-AR antagonist), but not prazosin (alpha1-AR antagonist), antagonized surgical trauma induced pro-inflammatory cytokine production in microglia cells isolated from rats. beta-AR activation in the absence of pro-inflammatory stimuli increased IL-1beta, TNF-alpha and IL-6 mRNA and protein expressions in the primary microglia cell culture. Isoproterenol (beta-AR agonist) treatment induced a time- and concentration-dependent increase of IL-1beta in cells. Both ERK1/2 and P38 MAPK inhibitor, but not PKA and JNK1/2 inhibitor abrogated isoproterenol-induced IL-1beta and IL-6 production in microglia cells. In conclusion, the results suggest that beta-ARs possess pro-inflammatory properties by modulating the functions of microglia cell.
Wang
Jun
J
Department of Integrative Medicine and Neurobiology, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, China. jwangf@shmu.edu.cn
Li
Jing
J
Sheng
Xiao
X
Zhao
Hui
H
Cao
Xiao-Ding
XD
Wang
Yan-Qing
YQ
Wu
Gen-Cheng
GC
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D008297:Male; D017628:Microglia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D011183:Postoperative Complications / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D016207:Cytokines; D018836:Inflammation Mediators; D011943:Receptors, Adrenergic, beta