Chemokines and Their Receptors in Chronic Pulmonary Disease

Lukacs, Nicholas W.; Hogaboam, Cory M.; Kunkel, Steven L.

doi:10.2174/1568010054022088

Cited by 33 publications

(13 citation statements)

References 89 publications

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“…Increased airway narrowing is a hallmark symptom of clinically important diseases such as asthma (24,25,37,43,45,47,50). The potential role of caveolae and their constituent caveolin proteins in regulation of [Ca 2ϩ ] i and force in ASM in health and diseases such as asthma and airway inflammation is an emerging area of research.…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1 and force regulation in porcine airway smooth muscle

Sathish¹,

Yang²,

Meuchel

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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We recently demonstrated the presence of caveolae in human airway smooth muscle (ASM) and the contribution of caveolin-1 to intracellular calcium ([Ca 2ϩ ]i) regulation. In the present study, we tested the hypothesis that caveolin-1 regulates ASM contractility. We examined the role of caveolins in force regulation of porcine ASM under control conditions as well as TNF-␣-induced airway inflammation. In porcine ASM strips, exposure to 10 mM methyl-␤-cyclodextrin (CD) or 5 M of the caveolin-1 specific scaffolding domain inhibitor peptide (CSD) resulted in time-dependent decrease in force responses to 1 M ACh. Overnight exposure to the cytokine TNF-␣ (50 ng/ml) accelerated and increased caveolin-1 expression and enhanced force responses to ACh. Suppression of caveolin-1 with small interfering RNA mimicked the effects of CD or CSD. Regarding mechanisms by which caveolae contribute to contractile changes, inhibition of MAP kinase with 10 M PD98059 did not alter control or TNF-␣-induced increases in force responses to ACh. However, inhibiting RhoA with 100 M fasudil or 10 M Y27632 resulted in significant decreases in force responses, with lesser effects in TNF-␣ exposed samples. Furthermore, Ca 2ϩ sensitivity for force generation was substantially reduced by fasudil or Y27632, an effect even more enhanced in the absence of caveolin-1 signaling. Overall, these results indicate that caveolin-1 is a critical player in enhanced ASM contractility with airway inflammation. caveolae; lung; inflammation; cytokine; MAP kinase; RhoA; small interfering RNA CAVEOLAE, FLASK-SHAPED PLASMA membrane invaginations rich in cholesterol and sphingolipids, express any of three caveolin proteins (caveolin-1, caveolin-2, and/or caveolin-3). By virtue of caveolar expression of agonist receptors, ion channels, and other membrane proteins, as well as the association of caveolins with intracellular proteins, the role of caveolins as organizers and facilitators of signal transduction is now well recognized (12,23,38,62,67,81,82).Multiple studies including our own (16,28,33,61,68,73), have now demonstrated the presence of caveolae and caveolins in airway smooth muscle (ASM

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Section: Discussionmentioning

confidence: 99%

Caveolin-1 and force regulation in porcine airway smooth muscle

Sathish¹,

Yang²,

Meuchel

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Chemokines play an important role in the recruitment of inflammatory cells from the circulation to the airways in both asthma and COPD (87). There has been particular interest in the role of chemokines in asthma and COPD, as they signal through GPCRs, for which small molecule antagonists can be relatively easily developed (88).…”

Section: Chemokinesmentioning

confidence: 99%

The cytokine network in asthma and chronic obstructive pulmonary disease

Barnes¹

2008

J. Clin. Invest.

828

714

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Asthma and chronic obstructive pulmonary disease (COPD) are very common inflammatory diseases of the airways. They both cause airway narrowing and are increasing in incidence throughout the world, imposing enormous burdens on health care. Cytokines play a key role in orchestrating the chronic inflammation and structural changes of the respiratory tract in both asthma and COPD and have become important targets for the development of new therapeutic strategies in these diseases. IntroductionThe most common inflammatory diseases of the airways are asthma and chronic obstructive pulmonary disease (COPD), and the incidence of both is increasing throughout the world. The prevalence of asthma in developed countries is approximately 10% in adults and even higher in children, whereas in developing countries, the prevalence is lower but increasing rapidly. The global prevalence of COPD is approximately 10% among individuals over the age of 40 years. Asthma often starts in early childhood and is characterized by intermittent wheezing and shortness of breath. In contrast, the predominant symptom in COPD is shortness of breath on exertion, which is persistent and slowly progressive. Although the clinical symptoms of both diseases are caused by airway narrowing as a result of inflammation in the airways, there are marked differences in the patterns of underlying inflammation.Cytokines play a key role in orchestrating the chronic inflammation of asthma and COPD by recruiting, activating, and promoting the survival of multiple inflammatory cells in the respiratory tract (Figure 1, Figure 2, and Table 1). Over 50 cytokines have now been identified in asthma and COPD, but their role in the pathophysiology of these complex airway diseases is often unclear. For the purpose of this Review, cytokines are classified into lymphokines (cytokines that are secreted by T cells and regulate immune responses), proinflammatory cytokines (cytokines that amplify and perpetuate the inflammatory process), growth factors (cytokines that promote cell survival and result in structural changes in the airways), chemokines (cytokines that are chemotactic for inflammatory cells), and antiinflammatory cytokines (cytokines that negatively modulate the inflammatory response), although many of these functions may overlap. Where possible, I have focused on human studies and have emphasized any therapeutic interventions that have been made.

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“…Inflammatory cell recruitment is mediated by leukotriene B 4 and by small peptides known as chemokines, which act by stimulating membrane receptors coupled to G proteins [53,54]. More than 50 chemokines, classified as C, CC, CXC and CX3C, activate more than 20 known membrane receptors [55]; some activate a single type of receptor, while others can activate several. Receptor activation stimulates the signal transduction pathways underlying chemotaxis and also proliferation, differentiation and survival of inflammatory cells.…”

Section: Copd and Inflammation: New Data For New Treatmentsmentioning

confidence: 99%

Beyond corticosteroids: future prospects in the management of inflammation in COPD

Roche¹,

Marthan²,

Berger³

et al. 2011

Eur Respir Rev

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Inflammation plays a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Exposure to cigarette smoke induces the recruitment of inflammatory cells in the airways and stimulates innate and adaptive immune mechanisms. Airway inflammation is involved in increased bronchial wall thickness, increased bronchial smooth muscle tone, mucus hypersecretion and loss of parenchymal elastic structures. Oxidative stress impairs tissue integrity, accelerates lung ageing and reduces the efficacy of corticosteroids by decreasing levels of histone deacetylase-2. Protease-antiprotease imbalance impairs tissues and is involved in inflammatory processes. Inflammation is also present in the pulmonary artery wall and at the systemic level in COPD patients, and may be involved in COPD-associated comorbidities.Proximal airways inflammation contributes to symptoms of chronic bronchitis while distal and parenchymal inflammation relates to airflow obstruction, emphysema and hyperinflation. Basal levels of airways and systemic inflammation are increased in frequent exacerbators.Inhaled corticosteroids are much less effective in COPD than in asthma, which relates to the intrinsically poor reversibility of COPD-related airflow obstruction and to molecular mechanisms of resistance relating to oxidative stress. Ongoing research aims at developing new drugs targeting more intimately COPD-specific mechanisms of inflammation, hypersecretion and tissue destruction and repair. Among new anti-inflammatory agents, phosphodiesterase-4 inhibitors have been the first to emerge.

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Chemokines and Their Receptors in Chronic Pulmonary Disease

Cited by 33 publications

References 89 publications

Caveolin-1 and force regulation in porcine airway smooth muscle

Caveolin-1 and force regulation in porcine airway smooth muscle

The cytokine network in asthma and chronic obstructive pulmonary disease

Beyond corticosteroids: future prospects in the management of inflammation in COPD

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