title: Immune/Inflammatory Response and Hypocontractility of Rabbit Colonic Smooth Muscle After TNBS-Induced Colitis.
abstract: The contractility of colonic smooth muscle is dysregulated due to immune/inflammatory responses in inflammatory bowel diseases. Inflammation in vitro induces up-regulation of regulator of G-protein signaling 4 (RGS4) expression in colonic smooth muscle cells.
  
  
  
  To characterize the immune/inflammatory responses and RGS4 expression pattern in colonic smooth muscle after induction of colitis.
  
  
  
  Colitis was induced in rabbits by intrarectal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Innate/adaptive immune response RT-qPCR array was performed using colonic circular muscle strips. At 1-9 weeks after colonic intramuscular microinjection of lentivirus, the distal and proximal colons were collected, and muscle strips and dispersed muscle cells were prepared from circular muscle layer. Expression levels of RGS4 and NFκB signaling components were determined by Western blot analysis. The biological consequences of RGS4 knockdown were assessed by measurement of muscle contraction and phospholipase C (PLC)-β activity in response to acetylcholine (ACh).
  
  
  
  Contraction in response to ACh was significantly inhibited in the inflamed colonic circular smooth muscle cells. RGS4, IL-1, IL-6, IL-8, CCL3, CD1D, and ITGB2 were significantly up-regulated, while IL-18, CXCR4, CD86, and C3 were significantly down-regulated in the inflamed muscle strips. RGS4 protein expression in the inflamed smooth muscles was dramatically increased. RGS4 stable knockdown in vivo augmented ACh-stimulated PLC-β activity and contraction in colonic smooth muscle cells.
  
  
  
  Inflamed smooth muscle exhibits up-regulation of IL-1-related signaling components, Th1 cytokines and RGS4, and inhibition of contraction. Stable knockdown of endogenous RGS4 in colonic smooth muscle increases PLC-β activity and contractile responses.
authors.affiliation: Department of Neuroscience, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA, 19140, USA.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neuroscience, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA, 19140, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Neuroscience, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA, 19140, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neuroscience, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA, 19140, USA.
authors.forename: Chaoran
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital, Guangxi Medical University, No. 6 Shuangyong Rd, Nanning, 530021, Guangxi, China.
authors.forename: JieAn
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Physiology and Biophysics, Medical College of Virginia Campus, Virginia Commonwealth University, 1101 East Marshall Street, Richmond, VA, 23298, USA.
authors.forename: Sunila
authors.initials: S
authors.lastname: Mahavadi
authors.affiliation: Department of Physiology and Biophysics, Medical College of Virginia Campus, Virginia Commonwealth University, 1101 East Marshall Street, Richmond, VA, 23298, USA.
authors.forename: Karnam S
authors.initials: KS
authors.lastname: Murthy
authors.affiliation: Department of Neuroscience, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA, 19140, USA. whu@temple.edu.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Hu
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D009119:Muscle Contraction / Q000276:immunology*; D009130:Muscle, Smooth / Q000473:pathology*; D011817:Rabbits; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D014302:Trinitrobenzenesulfonic Acid
keywords: Colitis; Rabbit; Regulators of G-protein signaling; Smooth muscle cells; shRNA