help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on February 5, 2004, doi:10.1165/rcmb.2003-0380OC

Am. J. Respir. Cell Mol. Biol., Volume 31, Number 1, July 2004, 92-99

A more recent version of this article appeared on July 1, 2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2003-0380OCv1
31/1/92    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wilkinson, T. S
Right arrow Articles by Wight, T. N
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wilkinson, T. S
Right arrow Articles by Wight, T. N

Submitted on October 24, 2003
Revised on February 5, 2004

Pro- and anti-inflammatory factors cooperate to control hyaluronan synthesis in lung fibroblasts

Thomas S Wilkinson1, Susan Potter-Perigo1, Christina Tsoi1, Leonard C Altman2, and Thomas N Wight3*

1 Vascular Biology, The Hope Heart Institute, Seattle, WA, USA, 2 Vascular Biology, The Hope Heart Institute, Seattle, WA, USA; Department of Medicine, Division of Allergy and Infectious Disease, University of Washington, Seattle, WA, USA, 3 Vascular Biology, The Hope Heart Institute, Seattle, WA, USA; Department of Pathology, University of Washington, Seattle, WA, USA

* To whom correspondence should be addressed. E-mail: twight{at}hopeheart.org.

Hyaluronan (HA) is an important constituent of the extracellular matrix and accumulates during inflammatory lung diseases like asthma. Little is known about the factors that regulate HA synthesis by lung cells. Accordingly, we investigated the effect of T-helper 1 (TH1) and 2 (TH2) cytokines and the anti-inflammatory agents fluticasone and salmeterol on HA synthesis in human lung fibroblasts. IL-1{beta} and TNF{alpha} were the most potent stimulators of HA synthesis and when combined, caused synergistic increases in HA accumulation. Time course analysis of HA accumulation and [3H]-glucosamine incorporation into HA demonstrated continued synthesis over the 24 hours of stimulation. Peak synthesis at 6-12 hours coincided with an increased proportion of high molecular weight HA. RT-PCR revealed that IL-1{beta} and TNF{alpha} induced hyaluronan synthase-2 mRNA three hours following stimulation and remained elevated throughout the 24-hour stimulation period. Fluticasone, inhibited IL-1{beta} and TNF{alpha} induced HA synthesis (44.5%) while salmeterol had no effect. When combined, fluticasone and salmeterol inhibited HA synthesis to a greater extent (85.2%). Further, fluticasone attenuated IL-1{beta} and TNF{alpha} stimulated hyaluronan synthase-2 mRNA and the addition of salmeterol cooperatively enhanced this inhibition. These results indicate that enhanced synthesis of HA by the pro-inflammatory cytokines IL-1{beta} and TNF{alpha} can be abrogated by specific corticosteroid and {beta}2-blocker combinations shown to be effective in the treatment of asthma.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
H. Kawana, H. Karaki, M. Higashi, M. Miyazaki, F. Hilberg, M. Kitagawa, and K. Harigaya
CD44 Suppresses TLR-Mediated Inflammation
J. Immunol., March 15, 2008; 180(6): 4235 - 4245.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Kastner, G. J. Thomas, R. H. Jenkins, M. Davies, and R. Steadman
Hyaluronan Induces the Selective Accumulation of Matrix- and Cell-Associated Proteoglycans by Mesangial Cells
Am. J. Pathol., December 1, 2007; 171(6): 1811 - 1821.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
C. Y. Han, S. Subramanian, C. K. Chan, M. Omer, T. Chiba, T. N. Wight, and A. Chait
Adipocyte-Derived Serum Amyloid A3 and Hyaluronan Play a Role in Monocyte Recruitment and Adhesion
Diabetes, September 1, 2007; 56(9): 2260 - 2273.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Guo, D. Kanter, M. L. Funderburgh, M. M. Mann, Y. Du, and J. L. Funderburgh
A Rapid Transient Increase in Hyaluronan Synthase-2 mRNA Initiates Secretion of Hyaluronan by Corneal Keratocytes in Response to Transforming Growth Factor beta
J. Biol. Chem., April 27, 2007; 282(17): 12475 - 12483.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Monslow, J. D. Williams, D. J. Fraser, D. R. Michael, P. Foka, A. P. Kift-Morgan, D. D. Luo, C. A. Fielding, K. J. Craig, N. Topley, et al.
Sp1 and Sp3 Mediate Constitutive Transcription of the Human Hyaluronan Synthase 2 Gene
J. Biol. Chem., June 30, 2006; 281(26): 18043 - 18050.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
I. Rubio-Gayosso, S. H. Platts, and B. R. Duling
Reactive oxygen species mediate modification of glycocalyx during ischemia-reperfusion injury
Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2247 - H2256.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
L. Todorova, E. Gurcan, A. Miller-Larsson, and G. Westergren-Thorsson
Lung Fibroblast Proteoglycan Production Induced by Serum Is Inhibited by Budesonide and Formoterol
Am. J. Respir. Cell Mol. Biol., January 1, 2006; 34(1): 92 - 100.
[Abstract] [Full Text] [PDF]

Home page
 ERRHome page
C. W. Frevert and P. L. Sannes
Matrix proteoglycans as effector molecules for epithelial cell function
Eur. Respir. Rev., December 1, 2005; 14(97): 137 - 144.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
S. Baouz, J. Giron-Michel, B. Azzarone, M. Giuliani, F. Cagnoni, S. Olsson, R. Testi, G. Gabbiani, and G. W. Canonica
Lung myofibroblasts as targets of salmeterol and fluticasone propionate: inhibition of {alpha}-SMA and NF-{kappa}B
Int. Immunol., November 1, 2005; 17(11): 1473 - 1481.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2004 American Thoracic Society.