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Brain endocannabinoids modulate lung Inflammation during sepsis (1157.4)
Author(s) -
Peng Jianya,
Russo Vincenzo,
Gertzberg Nancy,
Neumann Paul,
Johnson Arnold,
Feleder Carlos
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1157.4
Subject(s) - rimonabant , endocannabinoid system , inflammation , tlr4 , cannabinoid receptor , lung , cannabinoid , sepsis , receptor , medicine , pharmacology , endocrinology , septic shock , lipopolysaccharide , chemistry , antagonist
Sepsis is a systemic inflammatory response caused by infection which can lead to shock and lung injury. Previous studies indicate that septic shock is mediated by brain endocannabinoid 1 (CB1) receptors. Hence, this study tested the hypothesis that the brain CB1 receptors regulate LPS‐induced lung inflammation. Male Sprague‐Dawley rats received an intracerebroventricular (ICV) injection of either the CB1 receptor antagonist Rimonabant (2 µg/kg) or vehicle, 5 minutes prior to IV injection of either LPS (5 mg/kg) or saline. Lungs were removed 0.5 h or 4 h after IV injection of LPS and isolated for assessment of pulmonary capillary pressure (Ppc), lung wet/dry weight ratio (W/D), TLR4 activation, α7nicotinic acetylcholine (α7nAch) pathway, IL‐6 and VCAM. LPS‐ 0.5 h induced a decrease in lung levels of IRAK1 and IκBα indicating activation of TLR4, and decreased phosphorylated Src‐Y416 family kinases (pSFK) and phosphorylated Raf1‐S259 (pRaf1) suggesting decreased α7nAch signaling all which were prevented by Rimonabant. In addition, Rimonabant prevented the LPS‐induced 4 h increase in the W/D/Ppc and IL‐6 and Rimonabant reduced the LPS induced increase in VCAM expression. The data indicates that the brain CB1 receptor mediates, in part, the lung inflammation response to LPS. Grant Funding Source : Supported by NIH R01 HL059901 to A. Johnson and NIH R15A1072744 to C. Feleder