title: Sinomenine protects against lipopolysaccharide-induced acute lung injury in mice via adenosine A(2A) receptor signaling.
abstract: Sinomenine (SIN) is a bioactive alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, which is widely used in the clinical treatment of rheumatoid arthritis (RA). However, its role in acute lung injury (ALI) is unclear. In this study, we investigate the role of SIN in lipopolysaccharide (LPS)-induced ALI in mice. After ALI, lung water content and histological signs of pulmonary injury were attenuated, whereas the PaO2/FIO2 (P/F) ratios were elevated significantly in the mice pretreated with SIN. Additionally, SIN markedly inhibited inflammatory cytokine TNF-α and IL-1β expression levels as well as neutrophil infiltration in the lung tissues of the mice. Microarray analysis and real-time PCR showed that SIN treatment upregulated adenosine A(2A) receptor (A(2A)R) expression, and the protective effect of SIN was abolished in A(2A)R knockout mice. Further investigation in isolated mouse neutrophils confirmed the upregulation of A(2A)R by SIN and showed that A(2A)R-cAMP-PKA signaling was involved in the anti-inflammatory effect of SIN. Taken together, these findings demonstrate an A(2A)R-associated anti-inflammatory effect and the protective role of SIN in ALI, which suggests a potential novel approach to treat ALI.
authors.affiliation: Department of Cardiothoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Xie
authors.initials: X
authors.lastname: He
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Zeng
authors.forename: Shuang-Shuang
authors.initials: SS
authors.lastname: Dai
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008070:Lipopolysaccharides; D051379:Mice; D018345:Mice, Knockout; D009019:Morphinans / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000172:deficiency / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects*; D032841:Sinomenium / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009019:Morphinans; D043705:Receptor, Adenosine A2A; D014409:Tumor Necrosis Factor-alpha; C009271:sinomenine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
references.citation: Am J Physiol Lung Cell Mol Physiol. 2012 Aug 1;303(3):L259-71
references.pmid: 22659881
references.citation: Physiology (Bethesda). 2009 Oct;24:298-306
references.pmid: 19815856
references.citation: Shock. 2012 Feb;37(2):156-63
references.pmid: 22249219
references.citation: Acta Med Okayama. 1976 Feb;30(1):1-20
references.pmid: 61710
references.citation: Angiogenesis. 2005;8(1):3-12
references.pmid: 16132613
references.citation: J Clin Invest. 2007 Nov;117(11):3445-52
references.pmid: 17932569
references.citation: J Ethnopharmacol. 2000 May;70(2):135-41
references.pmid: 10771203
references.citation: J Clin Invest. 2002 Dec;110(11):1703-16
references.pmid: 12464676
references.citation: Int J Immunopharmacol. 1996 Oct;18(10):529-43
references.pmid: 9080247
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Jun;292(6):L1335-44
references.pmid: 17293374
references.citation: J Neurochem. 2010 Jun;113(6):1536-44
references.pmid: 20367749
references.citation: Eur J Pharmacol. 2006 Mar 8;533(1-3):77-88
references.pmid: 16458886
references.citation: J Immunol. 2007 Jul 15;179(2):1254-63
references.pmid: 17617618
references.citation: Am J Physiol Lung Cell Mol Physiol. 2006 May;290(5):L1036-43
references.pmid: 16339780
references.citation: J Neurosci. 2010 Apr 21;30(16):5802-10
references.pmid: 20410132
references.citation: J Immunol. 2003 Jul 1;171(1):338-45
references.pmid: 12817016
references.citation: N Engl J Med. 2000 May 4;342(18):1334-49
references.pmid: 10793167
references.citation: Biochem Pharmacol. 1994 Aug 30;48(5):1050-2
references.pmid: 8093093
references.citation: J Clin Invest. 2002 Dec;110(11):1603-5
references.pmid: 12464663
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Apr;284(4):L663-70
references.pmid: 12495940
references.citation: J Ethnopharmacol. 2007 Nov 1;114(2):180-5
references.pmid: 17869461
references.citation: Transplantation. 2003 Apr 15;75(7):940-5
references.pmid: 12698077
references.citation: J Neurosci. 1999 Nov 1;19(21):9192-200
references.pmid: 10531422
references.citation: Neuroscience. 2008 Feb 19;151(4):1198-207
references.pmid: 18207647
references.citation: Planta Med. 1999 Feb;65(1):80-2
references.pmid: 10083851
references.citation: J Thorac Cardiovasc Surg. 2005 May;129(5):1137-43
references.pmid: 15867791
references.citation: Arzneimittelforschung. 1994 Nov;44(11):1223-6
references.pmid: 7848335
references.citation: Am J Physiol Lung Cell Mol Physiol. 2000 Dec;279(6):L1137-45
references.pmid: 11076804
references.citation: Biochem J. 2005 Nov 1;391(Pt 3):575-80
references.pmid: 16022683
references.citation: Int J Immunopharmacol. 1994 Aug;16(8):685-91
references.pmid: 7989137
references.citation: J Clin Invest. 1997 Feb 15;99(4):737-44
references.pmid: 9045878
references.citation: Crit Care Med. 2006 Apr;34(4):1273-5
references.pmid: 16550090
references.citation: Int Immunopharmacol. 2011 Mar;11(3):373-6
references.pmid: 21109035
references.citation: Nature. 2001 Dec 20-27;414(6866):916-20
references.pmid: 11780065
references.citation: N Engl J Med. 2005 Oct 20;353(16):1685-93
references.pmid: 16236739
references.citation: PLoS Biol. 2005 Jun;3(6):e174
references.pmid: 15857155
references.citation: Am J Physiol Lung Cell Mol Physiol. 2006 May;290(5):L849-55
references.pmid: 16361356
references.citation: Int Immunopharmacol. 2009 Jul;9(7-8):894-9
references.pmid: 19336263
references.citation: J Thorac Cardiovasc Surg. 2008 Jan;135(1):156-65
references.pmid: 18179933
references.citation: Circ Res. 2006 Sep 15;99(6):590-7
references.pmid: 16917093
references.citation: J Leukoc Biol. 2002 Nov;72(5):1027-36
references.pmid: 12429726
references.citation: Respir Res. 2009 Jun 26;10:58
references.pmid: 19558673
references.citation: J Leukoc Biol. 2008 Mar;83(3):447-55
references.pmid: 18160539
references.citation: J Clin Invest. 2008 Oct;118(10):3301-15
references.pmid: 18787641
references.citation: J Immunopharmacol. 1985;7(1):33-42
references.pmid: 3874242
references.citation: Int Immunopharmacol. 2007 May;7(5):637-45
references.pmid: 17386411
references.citation: J Surg Res. 2008 Sep;149(1):3-8
references.pmid: 17937935
references.citation: J Immunol. 2004 Jul 1;173(1):21-4
references.pmid: 15210754
references.citation: J Ethnopharmacol. 2005 Apr 8;98(1-2):37-43
references.pmid: 15763362
references.citation: Transplantation. 1996 Dec 27;62(12):1855-60
references.pmid: 8990376