Submitted on November 20, 2006
Accepted on July 16, 2007
Exposure of differentiated Airway Smooth Muscle cells to serum stimulates both induction of Hypoxia Inducible Factor-1
and airway responsiveness to ACh
Georgia Chachami1, Apostolia Apostolos Hatziefthimiou2, Panagiotis Liakos3, Maria G. Ioannou4, Georgios K. Koukoulis4, Sofia Bonanou3, Paschalis-Adam Molyvdas5, George Simos3, and Efrosyni Paraskeva2*
1 Lab. of Physiology, Medical School, Univ. of Thessaly, Larissa, Greece; Lab. of Biochemistry, Medical Scholl, Univ. of Thessaly, Larissa, Greece
2 Lab. of Physiology, Medical school, Univ. of Thessaly, Larissa, Greece
3 Lab. of Biochemistry, Medical Scholl, Univ. of Thessaly, Larissa, Greece
4 Dept. of Pathology, Medical School, Univ. of Thessaly, Larissa, Greece
5 Lab. of Physiology, Medical School, Univ. of Thessaly, Larissa, Greece
* To whom correspondence should be addressed. E-mail: fparaskeva{at}med.uth.gr.
Airway smooth muscle (ASM) cells are characterised by phenotypic plasticity and can switch between differentiated and proliferative phenotypes. In rabbit tracheal ASM cells that had been differentiated in vitro by serum starvation, the re-addition of FBS caused initiation of proliferation and induction of nuclear and transcriptionally active hypoxia inducible factor (HIF)-1
. In addition, FBS stimulated the induction of HIF-1 by the hypoxia-mimetic cobalt. Treatment with either actinomycin D, cycloheximide, the phosphatidylinositol-3 kinase (PI-3 K) inhibitors LY294002 or wortmannin, or the reactive oxygen species (ROS) scavenger diphenyleneiodonium (DPI) inhibited the FBS-dependent induction of HIF-1. These data indicate that, in differentiated ASM cells, FBS up-regulates HIF-1 by a transcription-, translation-, PI-3 K and ROS-dependent mechanism. Interestingly, addition of FBS and cobalt also induced HIF-1 in organ cultures of rabbit trachea strips and synergistically increased their contractile response to ACh suggesting that HIF-1 might be implicated in airway hypercontractility.
