FIZZ1 potentiates the carbachol-induced tracheal smooth muscle contraction.
FIZZ1 is an adipokine highly expressed under inflammatory conditions, and yet, little is known of its function. In this study we examine the expression and function of FIZZ1 in an ovalbumin mouse model of asthma. Trachea from naïve or ovalbumin-sensitised and -challenged mice were compared for transcriptional, functional and proteomic differences using gene microarrays, ex vivo tracheal contraction, immunohistochemistry and Western blot analysis. FIZZ1 was expressed in ovalbumin-treated, but not naïve, trachea. Naïve trachea incubated with recombinant FIZZ1 exhibited denuded epithelium and contractile hyperresponsiveness. The FIZZ1-incubated trachea also exhibited an associated increased expression of phospho-c-Raf, phospho-extracellular signal-regulated kinase 1/2, phospho-p38, MLCK and MLC-20. These data demonstrate that FIZZ1 regulates tracheal smooth muscle contraction through impairment of the epithelium and activation of the mitogen-activated protein kinase pathway in muscle.
Chen
H
H
Inflammation/Immunology, Pfizer Research, Cambridge, MA 02140, USA.
Jacobson
B A
BA
Mason
L
L
Wolf
S F
SF
Bowman
M R
MR
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology; D004195:Disease Models, Animal; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D018679:Cholinergic Agonists; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; C413576:Retnla protein, mouse; C082161:lipopolysaccharide A; D002217:Carbachol; D010047:Ovalbumin; D009219:Myosin-Light-Chain Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases