title: Interleukin 1β attenuates vascular α1 adrenergic receptors expression following lipopolysaccharide-induced endotoxemia in rabbits: involvement of JAK2-STAT3 pathway.
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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Liang
authors.forename: Guang-Ming
authors.initials: GM
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Liang-Ming
authors.initials: LM
authors.lastname: Liu
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D019446:Endotoxemia / Q000503:physiopathology*; D005260:Female; D053583:Interleukin-1beta / Q000502:physiology*; D053614:Janus Kinase 2 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000378:metabolism / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D018340:Receptors, Adrenergic, alpha-1; D050796:STAT3 Transcription Factor; D010656:Phenylephrine; D053614:Janus Kinase 2