Chronic inflammation is a characteristic feature of asthma. Multiple inflammatory mediators are released within the asthmatic lung, some of which may have detrimental effects on signal transduction pathways in airway smooth muscle. The effects of tumor necrosis factor (TNF)- on the expression and function of muscarinic receptors and guanine nucleotide-binding protein (G protein) -subunits were examined in human airway smooth muscle cells. Cultured human airway smooth muscle cells were incubated in serum-free culture medium for 72 h in the presence and absence of 10 ng/ml of TNF-, after which the cells were lysed and subjected to electrophoresis and G_i-2, G_q, and G_s protein subunits were detected by immunoblot analysis with specific antisera. TNF- treatment for 72 h significantly increased the expression of G_i-2 and G_q proteins and enhanced carbachol (10⁷ M)-mediated inhibition of adenylyl cyclase activity and inositol phosphate synthesis. These data provide new evidence demonstrating that TNF- not only increases expression of G_i-2 and G_q proteins but also augments the associated signal transduction pathways that would facilitate increased tone of airway smooth muscle.

cytokines; asthma; adenylyl cyclase; inositol phosphate

This article has been cited by other articles:

				K. Mizuta, Y. Osawa, F. Mizuta, D. Xu, and C. W. Emala Functional Expression of GABAB Receptors in Airway Epithelium Am. J. Respir. Cell Mol. Biol., September 1, 2008; 39(3): 296 - 304. [Abstract] [Full Text] [PDF]

				K. Mizuta, G. Gallos, D. Zhu, F. Mizuta, F. Goubaeva, D. Xu, R. A. Panettieri Jr., J. Yang, and C. W. Emala Sr. Expression and coupling of neurokinin receptor subtypes to inositol phosphate and calcium signaling pathways in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L523 - L534. [Abstract] [Full Text] [PDF]

				A. G. P. Guedes, J. A. Jude, J. Paulin, H. Kita, F. E. Lund, and M. S. Kannan Role of CD38 in TNF-{alpha}-induced airway hyperresponsiveness Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L290 - L299. [Abstract] [Full Text] [PDF]

				Y. Osawa, P. D. Yim, D. Xu, R. A. Panettieri, and C. W. Emala Raf-1 kinase mediates adenylyl cyclase sensitization by TNF-{alpha} in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1414 - L1421. [Abstract] [Full Text] [PDF]

				B. Liu, A. M. Freyer, and I. P. Hall Bradykinin activates calcium-dependent potassium channels in cultured human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L898 - L907. [Abstract] [Full Text] [PDF]

				Y. Osawa, D. Xu, D. Sternberg, J. R. Sonett, J. D'Armiento, R. A. Panettieri, and C. W. Emala Functional expression of the GABAB receptor in human airway smooth muscle Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L923 - L931. [Abstract] [Full Text] [PDF]

				T. Pertel, D. Zhu, R. A. Panettieri, N. Yamaguchi, C. W. Emala, and C. A. Hirshman Expression and muscarinic receptor coupling of Lyn kinase in cultured human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L492 - L500. [Abstract] [Full Text] [PDF]

				Y. Osawa, H. T. Lee, C. A. Hirshman, D. Xu, and C. W. Emala Lipopolysaccharide-induced sensitization of adenylyl cyclase activity in murine macrophages Am J Physiol Cell Physiol, January 1, 2006; 290(1): C143 - C151. [Abstract] [Full Text] [PDF]

				D. A. Deshpande, T. A. White, S. Dogan, T. F. Walseth, R. A. Panettieri, and M. S. Kannan CD38/cyclic ADP-ribose signaling: role in the regulation of calcium homeostasis in airway smooth muscle Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L773 - L788. [Abstract] [Full Text] [PDF]

				H. Chen, O. Tliba, C. R. Van Besien, R. A. Panettieri Jr., and Y. Amrani Selected Contribution: TNF-{alpha} modulates murine tracheal rings responsiveness to G-protein-coupled receptor agonists and KCl J Appl Physiol, August 1, 2003; 95(2): 864 - 872. [Abstract] [Full Text] [PDF]

				I. Hunter, H. J. Cobban, P. Vandenabeele, D. J. MacEwan, and G. F. Nixon Tumor Necrosis Factor-alpha -Induced Activation of RhoA in Airway Smooth Muscle Cells: Role in the Ca2+ Sensitization of Myosin Light Chain20 Phosphorylation Mol. Pharmacol., March 1, 2003; 63(3): 714 - 721. [Abstract] [Full Text] [PDF]

				W. Gogarten, K. S. Lindeman, C. A. Hirshman, and C. W. Emala Tumor Necrosis Factor Alpha Stimulates Adenylyl Cyclase Activity in Human Myometrial Cells Biol Reprod, March 1, 2003; 68(3): 751 - 757. [Abstract] [Full Text] [PDF]

				L. J. Janssen Ionic mechanisms and Ca2+ regulation in airway smooth muscle contraction: do the data contradict dogma? Am J Physiol Lung Cell Mol Physiol, June 1, 2002; 282(6): L1161 - L1178. [Abstract] [Full Text] [PDF]

				H. Hakonarson, E. Halapi, R. Whelan, J. Gulcher, K. Stefansson, and M. M. Grunstein Association Between IL-1beta /TNF-alpha -Induced Glucocorticoid-Sensitive Changes in Multiple Gene Expression and Altered Responsiveness in Airway Smooth Muscle Am. J. Respir. Cell Mol. Biol., December 1, 2001; 25(6): 761 - 771. [Abstract] [Full Text] [PDF]

				R. M. Pascual, C. K. Billington, I. P. Hall, R. A. Panettieri Jr., J. E. Fish, S. P. Peters, and R. B. Penn Mechanisms of cytokine effects on G protein-coupled receptor-mediated signaling in airway smooth muscle Am J Physiol Lung Cell Mol Physiol, December 1, 2001; 281(6): L1425 - L1435. [Abstract] [Full Text] [PDF]

				R. E. Lesh, C. W. Emala, H. T. Lee, D. Zhu, R. A. Panettieri, and C. A. Hirshman Inhibition of geranylgeranylation blocks agonist-induced actin reorganization in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L824 - L831. [Abstract] [Full Text] [PDF]

				D. Xu, C. Isaacs, I. P. Hall, and C. W. Emala Human airway smooth muscle expresses 7 isoforms of adenylyl cyclase: a dominant role for isoform V Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L832 - L843. [Abstract] [Full Text] [PDF]

				H. Yoshimura, K. A. Jones, W. J. Perkins, T. Kai, and D. O. Warner Calcium sensitization produced by G protein activation in airway smooth muscle Am J Physiol Lung Cell Mol Physiol, September 1, 2001; 281(3): L631 - L638. [Abstract] [Full Text] [PDF]

				N. Fukuda, C. Jayr, A. Lazrak, Y. Wang, R. Lucas, S. Matalon, and M. A. Matthay Mechanisms of TNF-{alpha} stimulation of amiloride-sensitive sodium transport across alveolar epithelium Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1258 - L1265. [Abstract] [Full Text] [PDF]

				C. W. Emala, J. Clancy-Keen, and C. A. Hirshman Decreased adenylyl cyclase protein and function in airway smooth muscle by chronic carbachol pretreatment Am J Physiol Cell Physiol, October 1, 2000; 279(4): C1008 - C1015. [Abstract] [Full Text] [PDF]

				K. Hotta, C. A. Hirshman, and C. W. Emala TNF-alpha increases transcription of Galpha i-2 in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, August 1, 2000; 279(2): L319 - L325. [Abstract] [Full Text] [PDF]

				H. T. Lee and C. W. Emala Adenosine attenuates oxidant injury in human proximal tubular cells via A1 and A2a adenosine receptors Am J Physiol Renal Physiol, May 1, 2002; 282(5): F844 - F852. [Abstract] [Full Text] [PDF]