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Jeffrey J. Fredberg - One of the best experts on this subject based on the ideXlab platform.

  • Airway Smooth Muscle tone increases actin filamentogenesis and contractile capacity
    American Journal of Physiology-lung Cellular and Molecular Physiology, 2020
    Co-Authors: Morgan Gazzola, Jeffrey J. Fredberg, Chan-young Park, Cyndi Henry, Katherine Lortie, Fatemeh Khadangi, Ynuk Bosse
    Abstract:

    Force adaptation of Airway Smooth Muscle (ASM) is a process whereby the presence of tone (i.e., a sustained contraction) increases the contractile capacity. For example, tone has been shown to incr...

  • Airway Smooth Muscle tone modulates mechanically induced cytoskeletal stiffening and remodeling
    Journal of Applied Physiology, 2005
    Co-Authors: Linhong Deng, Jeffrey J. Fredberg, Nigel J Fairbank, Darren J Cole, Geoffrey N Maksym
    Abstract:

    The application of mechanical stresses to the Airway Smooth Muscle (ASM) cell causes time-dependent cytoskeletal stiffening and remodeling (Deng L, Fairbank NJ, Fabry B, Smith PG, and Maksym GN. Am...

  • rheology of Airway Smooth Muscle cells is associated with cytoskeletal contractile stress
    Journal of Applied Physiology, 2004
    Co-Authors: Dimitrije Stamenovic, Ben Fabry, Jeffrey J. Fredberg, Béla Suki, Ning Wang, Julie E Buy
    Abstract:

    Recently reported data from mechanical measurements of cultured Airway Smooth Muscle cells show that stiffness of the cytoskeletal matrix is determined by the extent of static contractile stress bo...

  • role of heat shock protein 27 in cytoskeletal remodeling of the Airway Smooth Muscle cell
    Journal of Applied Physiology, 2004
    Co-Authors: Steven S An, William T Gerthoffer, Ben Fabry, Stephanie A Shore, Mathew Mellema, Predrag Bursac, Usamah S Kayyali, Matthias Gaestel, Jeffrey J. Fredberg
    Abstract:

    Remodeling of the Airway Smooth Muscle (ASM) cell has been proposed to play an important role in Airway hyperresponsiveness. Using a functional assay, we have assessed remodeling of the cultured ra...

  • rheology of Airway Smooth Muscle cells is associated with cytoskeletal contractile stress
    Journal of Applied Physiology, 2004
    Co-Authors: Dimitrije Stamenovic, Ben Fabry, Jeffrey J. Fredberg, Béla Suki, Ning Wang, Julie E Buy
    Abstract:

    Recently reported data from mechanical measurements of cultured Airway Smooth Muscle cells show that stiffness of the cytoskeletal matrix is determined by the extent of static contractile stress borne by the cytoskeleton (Wang N, Tolic-Norrelykke IM, Chen J, Mijailovich SM, Butler JP, Fredberg JJ, and Stamenovic D. Am J Physiol Cell Physiol 282, C606-C616, 2002). On the other hand, rheological measurements on these cells show that cytoskeletal stiffness changes with frequency of imposed mechanical loading according to a power law (Fabry B, Maksym GN, Butler JP, Glogauer M, Navajas DF, and Fredberg JJ. Phys Rev Lett 87: 148102, 2001). In this study, we examine the possibility that these two empirical observations might be interrelated. We combine previously reported data for contractile stress of human Airway Smooth Muscle cells with new data describing rheological properties of these cells and derive quantitative, mathematically tractable, and experimentally verifiable empirical relationships between contractile stress and indexes of cell rheology. These findings reveal an intriguing role of the contractile stress: although it maintains structural stability of the cell under applied mechanical loads, it may also regulate rheological properties of the cytoskeleton, which are essential for other cell functions.

Judith L. Black - One of the best experts on this subject based on the ideXlab platform.

  • Airway Smooth Muscle dynamics a common pathway of Airway obstruction in asthma
    European Respiratory Journal, 2007
    Co-Authors: Tony R Bai, Judith L. Black, Linhong Deng, Jason H T Bates, Robert H Brown, Vito Brusasco, Pasquale Chitano, Maria Dowell, David H Eidelman
    Abstract:

    Excessive Airway obstruction is the cause of symptoms and abnormal lung function in asthma. As Airway Smooth Muscle (ASM) is the effecter controlling Airway calibre, it is suspected that dysfunction of ASM contributes to the pathophysiology of asthma. However, the precise role of ASM in the series of events leading to asthmatic symptoms is not clear. It is not certain whether, in asthma, there is a change in the intrinsic properties of ASM, a change in the structure and mechanical properties of the noncontractile components of the Airway wall, or a change in the interdependence of the Airway wall with the surrounding lung parenchyma. All these potential changes could result from acute or chronic Airway inflammation and associated tissue repair and remodelling. Anti-inflammatory therapy, however, does not "cure" asthma, and Airway hyperresponsiveness can persist in asthmatics, even in the absence of Airway inflammation. This is perhaps because the therapy does not directly address a fundamental abnormality of asthma, that of exaggerated Airway narrowing due to excessive shortening of ASM. In the present study, a central role for Airway Smooth Muscle in the pathogenesis of Airway hyperresponsiveness in asthma is explored.

  • increased proinflammatory responses from asthmatic human Airway Smooth Muscle cells in response to rhinovirus infection
    Respiratory Research, 2006
    Co-Authors: Brian G Oliver, Janette K. Burgess, Michael Roth, Sebastian L Johnston, Melissa Baraket, Nicholas J C King, Sam Lim, Judith L. Black
    Abstract:

    Background Exacerbations of asthma are associated with viral respiratory tract infections, of which rhinoviruses (RV) are the predominant virus type. Airway Smooth Muscle is important in asthma pathogenesis, however little is known about the potential interaction of RV and human Airway Smooth Muscle cells (HASM). We hypothesised that rhinovirus induction of inflammatory cytokine release from Airway Smooth Muscle is augmented and differentially regulated in asthmatic compared to normal HASM cells.

  • Connective tissue growth factor induces extracellular matrix in asthmatic Airway Smooth Muscle.
    American journal of respiratory and critical care medicine, 2005
    Co-Authors: Peter R. A. Johnson, Janette K. Burgess, Maree H. Poniris, Sarah Boustany, Stephen M. Twigg, Judith L. Black
    Abstract:

    Transforming growth factor (TGF)-beta and connective tissue growth factor may be implicated in extracellular matrix protein deposition in asthma. We have recently reported that TGF-beta increased connective tissue growth factor expression in Airway Smooth Muscle cells isolated from patients with asthma. In this study, we examined fibronectin and collagen production and signal transduction pathways after stimulation with TGF-beta and connective tissue growth factor. In both asthmatic and nonasthmatic Airway Smooth Muscle cells, TGF-beta and connective tissue growth factor led to the production of fibronectin and collagen I. Fibronectin and collagen expression was extracellular regulated kinase-dependent in both cell types but phosphoinositide-3 kinase-dependent only in asthmatic Airway Smooth Muscle cells. p38 was implicated in fibronectin but not collagen expression in both cell types. TGF-beta induction of fibronectin and collagen was in part mediated by an autocrine action of connective tissue growth factor. Phosphorylation of SMAD-2 may represent an additional pathway because this was increased in asthmatic cells. Our results suggest that these two cytokines may be important in the deposition of extracellular matrix proteins and that the signal transduction pathways may be different in asthmatic and nonasthmatic cells.

  • the cxcl10 cxcr3 axis mediates human lung mast cell migration to asthmatic Airway Smooth Muscle
    American Journal of Respiratory and Critical Care Medicine, 2005
    Co-Authors: Christopher E Brightling, Judith L. Black, Davinder Kaur, Alaina J Ammit, A J Wardlaw, Margaret J Hughes, Peter Bradding
    Abstract:

    Mast cell microlocalization within the Airway Smooth Muscle bundle is an important determinant of the asthmatic phenotype. We hypothesized that mast cells migrate toward Airway Smooth Muscle in response to Smooth Muscle-derived chemokines. In this study, we investigated (1) chemokine receptor expression by mast cells in the Airway Smooth Muscle bundle in bronchial biopsies from subjects with asthma using immunohistology, (2) the concentration of chemokines in supernatants from stimulated ex vivo Airway Smooth Muscle cells from subjects with and without asthma measured by enzyme-linked immunosorbent assay, and (3) mast cell migration toward these supernatants using chemotaxis assays. We found that CXCR3 was the most abundantly expressed chemokine receptor on human lung mast cells in the Airway Smooth Muscle in asthma and was expressed by 100% of these mast cells compared with 47% of mast cells in the submucosa. Human lung mast cell migration was induced by Airway Smooth Muscle cultures predominantly through activation of CXCR3. Most importantly, CXCL10 was expressed preferentially by asthmatic Airway Smooth Muscle in bronchial biopsies and ex vivo cells compared with those from healthy control subjects. These results suggest that inhibition of the CXCL10/CXCR3 axis offers a novel target for the treatment of asthma.

  • cd40 and ox40 ligand are increased on stimulated asthmatic Airway Smooth Muscle
    The Journal of Allergy and Clinical Immunology, 2005
    Co-Authors: Peter R. A. Johnson, Janette K. Burgess, Sarah Boustany, Judith L. Black, A E Blake, Carol L Armour, Nicholas H Hunt
    Abstract:

    BACKGROUND: Severe, persistent asthma is characterized by Airway Smooth Muscle hyperplasia, inflammatory cell infiltration into the Smooth Muscle, and increased expression of many cytokines, including IL-4, IL-13, IL-1beta, and TNF-alpha. These cytokines have the potential to alter the expression of surface receptors such as CD40 and OX40 ligand on the Airway Smooth Muscle cell. OBJECTIVE: To examine whether cytokines alter expression of CD40 and OX40 ligand on Airway Smooth Muscle cells and identify any differences in response between asthmatic and nonasthmatic Airway Smooth Muscle cells. METHODS: We used flow cytometry and immunohistochemistry to detect CD40 and OX40 ligand on Airway Smooth Muscle cells cultured in the presence of TNF-alpha, IL-1beta, IL-4, or IL-13. Prostaglandin E 2 levels were assessed by ELISA. RESULTS: TNF-alpha increased expression of both CD40 and OX40 ligand on both asthmatic and nonasthmatic Airway Smooth Muscle cells. The level of expression was significantly greater on the asthmatic cells. IL-1beta alone had no effect, but it attenuated the TNF-induced expression of both CD40 and OX40 ligand. The mechanism of inhibition was COX-dependent for CD40 and was COX-independent but cyclic AMP-dependent for OX40 ligand. IL-4 and IL-13 had no effect. CONCLUSION: Our study has demonstrated that TNF-alpha and IL-1beta have the potential to modulate differentially the interactions between cells present in the inflamed Airways of a patient with asthma and therefore to contribute to the regulation of Airway inflammation and remodeling.

Y S Prakash - One of the best experts on this subject based on the ideXlab platform.

  • fetal human Airway Smooth Muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone
    Pediatric Research, 2015
    Co-Authors: Helen Pearson, Rodney D Britt, Christine M Pabelick, Y S Prakash, Yassine Amrani, Hitesh Pandya
    Abstract:

    Fetal human Airway Smooth Muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone

  • Airway Smooth Muscle in Airway reactivity and remodeling what have we learned
    American Journal of Physiology-lung Cellular and Molecular Physiology, 2013
    Co-Authors: Y S Prakash
    Abstract:

    It is now established that Airway Smooth Muscle (ASM) has roles in determining Airway structure and function, well beyond that as the major contractile element. Indeed, changes in ASM function are ...

  • friction in Airway Smooth Muscle mechanism latch and implications in asthma
    Journal of Applied Physiology, 1996
    Co-Authors: Jeffrey J. Fredberg, James P Butler, Keith A. Jones, Y S Prakash, Soufia Helioui Raboudi, Stephanie A Shore, M Nathan, Gary C Sieck
    Abstract:

    Fredberg, J. J., K. A. Jones, M. Nathan, S. Raboudi, Y. S. Prakash, S. A. Shore, J. P. Butler, and G. C. Sieck. Friction in Airway Smooth Muscle: mechanism, latch, and implications in asthma. J. Appl. Physiol. 81(6): 2703–2712, 1996.—In Muscle, active force and stiffness reflect numbers of actin-myosin interactions and shortening velocity reflects their turnover rates, but the molecular basis of mechanical friction is somewhat less clear. To better characterize molecular mechanisms that govern mechanical friction, we measured the rate of mechanical energy dissipation and the rate of actomyosin ATP utilization simultaneously in activated canine Airway Smooth Muscle subjected to small periodic stretches as occur in breathing. The amplitude of the frictional stress is proportional to ηE, where E is the tissue stiffness defined by the slope of the resulting force vs. displacement loop and η is the hysteresivity defined by the fatness of that loop. From contractile stimulus onset, the time course of frictional stress amplitude followed a biphasic pattern that tracked that of the rate of actomyosin ATP consumption. The time course of hysteresivity, however, followed a different biphasic pattern that tracked that of shortening velocity. Taken together with an analysis of mechanical energy storage and dissipation in the cross-bridge cycle, these results indicate, first, that like shortening velocity and the rate of actomyosin ATP utilization, mechanical friction in Airway Smooth Muscle is also governed by the rate of cross-bridge cycling; second, that changes in cycling rate associated with conversion of rapidly cycling cross bridges to slowly cycling latch bridges can be assessed from changes of hysteresivity of the force vs. displacement loop; and third, that steady-state force maintenance (latch) is a low-friction contractile state. This last finding may account for the unique inability of asthmatic patients to reverse spontaneous Airways obstruction with a deep inspiration.

Reynold A Panettieri - One of the best experts on this subject based on the ideXlab platform.

  • modulation of bronchomotor tone pathways in Airway Smooth Muscle function and bronchomotor tone in asthma
    Clinics in Chest Medicine, 2019
    Co-Authors: Cynthia J Koziolwhite, Reynold A Panettieri
    Abstract:

    : Airway Smooth Muscle is the primary cell mediating bronchomotor tone. The milieu created in the asthmatic lung modulates Airway Smooth Muscle contractility and relaxation. Experimental findings suggest intrinsic abnormalities in Airway Smooth Muscle derived from patients with asthma in comparison with Airway Smooth Muscle from those without asthma. These changes to excitation-contraction pathways may underlie Airway hyperresponsiveness and increased Airway resistance associated with asthma.

  • glucocorticoid and tnf signaling converge at a20 tnfaip3 to repress Airway Smooth Muscle cytokine expression
    American Journal of Physiology-lung Cellular and Molecular Physiology, 2016
    Co-Authors: Sarah K Sasse, Reynold A Panettieri, Mohammed O Altonsy, Vineela Kadiyala, Anthony N Gerber
    Abstract:

    Airway Smooth Muscle is a major target tissue for glucocorticoid (GC)-based asthma therapies, however, molecular mechanisms through which the GC receptor (GR) exerts therapeutic effects in this key...

  • relaxation of human Airway Smooth Muscle cells 1174 1
    The FASEB Journal, 2014
    Co-Authors: Robert S Fitzgerald, Reynold A Panettieri, Rui Wang, Steven S An
    Abstract:

    The purpose of this study was to determine if H2S relaxed human Airway Smooth Muscle cells. If so, we explored the mechanisms responsible for the phenomenon. Human Airway Smooth Muscle cells (HASM) were prepared from human bronchi obtained from lungs unsuitable for transplantation. Dynamic changes in stiffness were measured as an indicator of contraction and relaxation of isolated HASM, using Magnetic Twisting Cytometry (MTC). Acute exposure of the cells to two agents capable of generating H2S, Na2S and GYY4137, decreased cell stiffness in a dose-dependent fashion, with maximal relaxation at 10mM and 5mM, respectively. In addition, cells exposed to varying doses of GYY4137 for 24 hours exhibited dose-dependent decreases in cell stiffness that were substantially greater than acute responses (21% relaxation at 300s vs 50% relaxation at 24h). We further determined that, like vascular Smooth Muscle, HASM exhibited the presence of ATP-sensitive K channels and the H2S synthesizing enzyme, cystathionine-g-lyase....

  • Mechanisms of Acute Desensitization of the � 2AR–Adenylyl Cyclase Pathway in Human Airway Smooth Muscle
    2013
    Co-Authors: Raymond B Penn, Reynold A Panettieri, Jeffrey L Benovic, Department Of Microbiology
    Abstract:

    � 2-Adrenergic receptors ( � 2ARs) are important regulators of Airway Smooth Muscle tone, and �-sympathomimetic drugs are the most widely used agents in asthma therapy and are universally recognized as the treatment of choice for acute asthma attacks. Despite the clinical importance of �-agonists and a good understanding of their mechanism of action in Airway Smooth Muscle relaxation, surprisingly little is known about the manner in which the � 2AR signaling pathway is regulated in human Airway Smooth Muscle (HASM). In this communication, we characterize mechanisms underlying rapid desensitization of the HASM � 2AR–adenylyl cyclase (AC) pathway. Acute homologous desensitization of � 2AR-mediated cyclic adenosine monophosphate (cAMP) production was characterized by an � 60 % loss of maximal responsiveness to isoproterenol (ISO) when cells were pretreated for 30 min with 1 �M ISO. Acute heterologous � 2AR desensitization was characterized by an � 20 % and 30 % loss of maximal responsiveness to ISO challenge when cells were pretreated with forskolin and prostaglandin E 2 (PGE 2), respectively. Each form of desensitization was also characterized by an increase in the EC 50 for ISO. � 2AR sequestration was associated with but not required for homologous desensitization. However, sequestration was required for rapid resensitization. Minimal alterations in inherent AC activity were observed with both modes of desensitization, suggesting that the � 2AR is the principal locus of regulation. Protein kinase inhibition by staurosporin

  • raf 1 actin dynamics and abelson tyrosine kinase in human Airway Smooth Muscle cells
    American Journal of Respiratory Cell and Molecular Biology, 2013
    Co-Authors: Ruping Wang, Reynold A Panettieri, Orion P Mercaitis, Li Jia, Dale D Tang
    Abstract:

    Raf-1 is a serine/threonine protein kinase that has an essential role in cell proliferation. The mechanisms that regulate Raf-1 in Airway Smooth Muscle are not well understood. In this study, treatment with platelet-derived growth factor (PDGF) induced spatial redistribution of Raf-1 from the cytoplasm to the periphery of human Airway Smooth Muscle cells. Moreover, a pool of Raf-1 was found in F-actin of human Airway Smooth Muscle cells. Activation with PDGF led to an increase in the association of Raf-1 with cytoskeletal actin. Treatment of cells with the actin polymerization inhibitor latrunculin A (LAT-A), but not the microtubule depolymerizer nocodazole, inhibited the interaction of Raf-1 with actin in response to PDGF activation. Because abelson tyrosine kinase (Abl) is known to specifically regulate actin dynamics in Smooth Muscle, the role of Abl in modulating the coupling of Raf-1 with actin was also evaluated. Abl knockdown by RNA interference attenuated the association of Raf-1 with actin, which...

Janette K. Burgess - One of the best experts on this subject based on the ideXlab platform.

  • treating asthma means treating Airway Smooth Muscle cells
    European Respiratory Journal, 2008
    Co-Authors: Suzanne Zuyderduyn, Maria B Sukkar, A Fust, S Dhaliwal, Janette K. Burgess
    Abstract:

    Asthma is characterised by Airway hyperresponsiveness, Airway inflammation and Airway remodelling. Airway Smooth Muscle cells are known to be the main effector cells of Airway narrowing. In the present paper, studies will be discussed that have led to a novel view of the role of Airway Smooth Muscle in the pathogenesis of asthma in which Airway hyperresponsiveness, remodelling and inflammation are, at least in part, attributable to Airway Smooth Muscle. Furthermore, how this new view may lead to a change in the phenotyping and treatment of patients with asthma will be discussed.

  • increased proinflammatory responses from asthmatic human Airway Smooth Muscle cells in response to rhinovirus infection
    Respiratory Research, 2006
    Co-Authors: Brian G Oliver, Janette K. Burgess, Michael Roth, Sebastian L Johnston, Melissa Baraket, Nicholas J C King, Sam Lim, Judith L. Black
    Abstract:

    Background Exacerbations of asthma are associated with viral respiratory tract infections, of which rhinoviruses (RV) are the predominant virus type. Airway Smooth Muscle is important in asthma pathogenesis, however little is known about the potential interaction of RV and human Airway Smooth Muscle cells (HASM). We hypothesised that rhinovirus induction of inflammatory cytokine release from Airway Smooth Muscle is augmented and differentially regulated in asthmatic compared to normal HASM cells.

  • Connective tissue growth factor induces extracellular matrix in asthmatic Airway Smooth Muscle.
    American journal of respiratory and critical care medicine, 2005
    Co-Authors: Peter R. A. Johnson, Janette K. Burgess, Maree H. Poniris, Sarah Boustany, Stephen M. Twigg, Judith L. Black
    Abstract:

    Transforming growth factor (TGF)-beta and connective tissue growth factor may be implicated in extracellular matrix protein deposition in asthma. We have recently reported that TGF-beta increased connective tissue growth factor expression in Airway Smooth Muscle cells isolated from patients with asthma. In this study, we examined fibronectin and collagen production and signal transduction pathways after stimulation with TGF-beta and connective tissue growth factor. In both asthmatic and nonasthmatic Airway Smooth Muscle cells, TGF-beta and connective tissue growth factor led to the production of fibronectin and collagen I. Fibronectin and collagen expression was extracellular regulated kinase-dependent in both cell types but phosphoinositide-3 kinase-dependent only in asthmatic Airway Smooth Muscle cells. p38 was implicated in fibronectin but not collagen expression in both cell types. TGF-beta induction of fibronectin and collagen was in part mediated by an autocrine action of connective tissue growth factor. Phosphorylation of SMAD-2 may represent an additional pathway because this was increased in asthmatic cells. Our results suggest that these two cytokines may be important in the deposition of extracellular matrix proteins and that the signal transduction pathways may be different in asthmatic and nonasthmatic cells.

  • cd40 and ox40 ligand are increased on stimulated asthmatic Airway Smooth Muscle
    The Journal of Allergy and Clinical Immunology, 2005
    Co-Authors: Peter R. A. Johnson, Janette K. Burgess, Sarah Boustany, Judith L. Black, A E Blake, Carol L Armour, Nicholas H Hunt
    Abstract:

    BACKGROUND: Severe, persistent asthma is characterized by Airway Smooth Muscle hyperplasia, inflammatory cell infiltration into the Smooth Muscle, and increased expression of many cytokines, including IL-4, IL-13, IL-1beta, and TNF-alpha. These cytokines have the potential to alter the expression of surface receptors such as CD40 and OX40 ligand on the Airway Smooth Muscle cell. OBJECTIVE: To examine whether cytokines alter expression of CD40 and OX40 ligand on Airway Smooth Muscle cells and identify any differences in response between asthmatic and nonasthmatic Airway Smooth Muscle cells. METHODS: We used flow cytometry and immunohistochemistry to detect CD40 and OX40 ligand on Airway Smooth Muscle cells cultured in the presence of TNF-alpha, IL-1beta, IL-4, or IL-13. Prostaglandin E 2 levels were assessed by ELISA. RESULTS: TNF-alpha increased expression of both CD40 and OX40 ligand on both asthmatic and nonasthmatic Airway Smooth Muscle cells. The level of expression was significantly greater on the asthmatic cells. IL-1beta alone had no effect, but it attenuated the TNF-induced expression of both CD40 and OX40 ligand. The mechanism of inhibition was COX-dependent for CD40 and was COX-independent but cyclic AMP-dependent for OX40 ligand. IL-4 and IL-13 had no effect. CONCLUSION: Our study has demonstrated that TNF-alpha and IL-1beta have the potential to modulate differentially the interactions between cells present in the inflamed Airways of a patient with asthma and therefore to contribute to the regulation of Airway inflammation and remodeling.

  • expression of connective tissue growth factor in asthmatic Airway Smooth Muscle cells
    American Journal of Respiratory and Critical Care Medicine, 2003
    Co-Authors: Janette K. Burgess, Peter R. A. Johnson, Maree H. Poniris, Brent E Mcparland, G G King, Michael Roth, Judith L. Black
    Abstract:

    There is strong evidence to implicate transforming growth factor-beta in the remodeling that occurs in asthma, as levels are increased in bronchial lavage fluid and gene expression is increased in bronchial tissue. Transforming growth factor-beta is also known to increase the release of collagen from Airway Smooth Muscle. Here we identify for the first time a possible mechanism for the effects of transforming growth factor-beta. Transforming growth factor-beta specifically induces mRNA and protein for connective tissue growth factor in Airway Smooth Muscle, and moreover, we report that the connective tissue growth factor response is greater in Airway Smooth Muscle cultured from patients with asthma compared with patients without asthma. This occurs at both the level of mRNA (37.53 +/- 11.62- and 13.59 +/- 3.12-fold increase at 24 hours compared with time 0, respectively, p < 0.02) and protein production (67.57 +/- 27.80- and 3.58 +/- 0.6-fold increase at 24 hours compared with time 0, respectively, p < 0.03). The differential connective tissue growth factor response to transforming growth factor-beta in asthmatic Airway Smooth Muscle identifies a potential role for connective tissue growth factor in the remodeling that is characteristic of severe persistent asthma.