Jia-Lin Liang1, Guang-Ming Yang, Tao Li, Liang-Ming Liu. 1. From the State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing People's Republic of China.
Abstract
BACKGROUND: Studies have shown that interleukin 1β (IL-1β) participates in the down-regulation of vascular reactivity via both nitric oxide-dependent and nitric oxide-independent mechanisms during shock. However, the precise mechanisms of nitric oxide-independent pathway remain to be established. METHODS: The effect of IL-1β on the expression of α1 adrenergic receptors (α1AR) and the relationship with Janus kinase 2-signal transducer and activator of transcription 3 (JAK2-STAT3) pathway were observed using a rabbit model of lipopolysaccharide (LPS)-induced endotoxemia and superior mesenteric arteries (SMAs) in vivo and in vitro, respectively. RESULTS: The vascular reactivity of SMAs to α1AR agonist (phenylephrine) displayed a biphasic change after LPS (significantly increased at 0.5 hour following LPS and then markedly decreased after 2 hours), the α1A, α1B and α1DAR messenger RNA (mRNA) and protein expression seemed a time-dependent decrease following LPS administration, α1A and α1DAR decreased more obviously than α1BAR. IL-1ra (4 µg/mL) partly reversed LPS-induced the decrease of vascular reactivity and down-regulation of α1AR expression. In vitro incubation with IL-1β (12.5-50 ng/mL) significantly decreased the vascular reactivity of SMA to phenylephrine and the expression of α1AR mRNA and protein and elevated the DNA binding ability of STAT3. AG490 (10 µmol/L), an inhibitor of JAK2, partly reversed the IL-1β-induced down-regulation of vascular reactivity and α1AR mRNA and protein expression and suppressed the DNA binding ability of STAT3. CONCLUSION: IL-1β participates in the regulation of vascular hyporeactivity following endotoxemia in rabbit. The mechanism is related to the down-regulation of α1AR expression through activating the JAK2-STAT3 pathway.
BACKGROUND: Studies have shown that interleukin 1β (IL-1β) participates in the down-regulation of vascular reactivity via both nitric oxide-dependent and nitric oxide-independent mechanisms during shock. However, the precise mechanisms of nitric oxide-independent pathway remain to be established. METHODS: The effect of IL-1β on the expression of α1 adrenergic receptors (α1AR) and the relationship with Janus kinase 2-signal transducer and activator of transcription 3 (JAK2-STAT3) pathway were observed using a rabbit model of lipopolysaccharide (LPS)-induced endotoxemia and superior mesenteric arteries (SMAs) in vivo and in vitro, respectively. RESULTS: The vascular reactivity of SMAs to α1AR agonist (phenylephrine) displayed a biphasic change after LPS (significantly increased at 0.5 hour following LPS and then markedly decreased after 2 hours), the α1A, α1B and α1DAR messenger RNA (mRNA) and protein expression seemed a time-dependent decrease following LPS administration, α1A and α1DAR decreased more obviously than α1BAR. IL-1ra (4 µg/mL) partly reversed LPS-induced the decrease of vascular reactivity and down-regulation of α1AR expression. In vitro incubation with IL-1β (12.5-50 ng/mL) significantly decreased the vascular reactivity of SMA to phenylephrine and the expression of α1AR mRNA and protein and elevated the DNA binding ability of STAT3. AG490 (10 µmol/L), an inhibitor of JAK2, partly reversed the IL-1β-induced down-regulation of vascular reactivity and α1AR mRNA and protein expression and suppressed the DNA binding ability of STAT3. CONCLUSION: IL-1β participates in the regulation of vascular hyporeactivity following endotoxemia in rabbit. The mechanism is related to the down-regulation of α1AR expression through activating the JAK2-STAT3 pathway.
Authors: Ahmed M Adlan; Jet J C S Veldhuijzen van Zanten; Gregory Y H Lip; Julian F R Paton; George D Kitas; James P Fisher Journal: Auton Neurosci Date: 2017-09-13 Impact factor: 3.145