Autocrine regulation of asthmatic airway inflammation: role of airway smooth muscle

Abstract

ASM = airway smooth muscle; BAL = bronchoalveolar lavage; COX = cyclooxygenase; ECM = extracellular matrix; FGF = fibroblast growth factor; GM-CSF = granulocyte/macrophage-colony stimulating factor; IFN = interferon; IGF = insulin-like growth factor; IL = interleukin; LIF = leukaemia inhibitory factor; 5-LO = 5-lipoxygenase; LT = leukotriene; MCP = monocyte chemotactic protein; MHC = major histocompatibility complex; NO = nitric oxide; PDGF = platelet-derived growth factor; PG = prostaglandin; RANTES = regulated on activation, normal T cell expressed and secreted; TGF = transforming growth factor; Th = T helper cells; TNF-α = tumour necrosis factor-α; TX = thromboxane. Available online http://respiratory-research.com/content/3/1/11 IntroductionInflammation of the airway wall is a central characteristic of asthma [1]. Airborne allergens often lead to an accumulation of eosinophils, lymphocytes (predominantly CD4 type), mast cells and macrophages, resulting in an inflammatory reaction in the mucosa. Neutrophil numbers can increase during an exacerbation. The release of mediators from these inflammatory cells has been proposed to contribute directly or indirectly to changes in airway structure and function.Important structural changes of inflamed airways include epithelial cell shedding, basement membrane thickening, goblet cell hyperplasia (increase in cell number) and hypertrophy (increase in cell size), as well as an increase in airway smooth muscle (ASM) content [2]. These structural changes consequently form the basis for airway remodelling, a phenomenon believed to have profound consequences for airway function [3]. Bronchial vascular remodelling, with an increase in size and number of blood vessels as well as vascular hyperaemia have been proposed as contributing factors in airway wall remodelling in patients with chronic asthma.The ASM has been typically described as a contractile tissue, responding to pro-inflammatory mediators and neurotransmitters by contracting, and responding to bronchodilators by relaxing. It has recently been recognised, AbstractChronic airway inflammation is one of the main features of asthma. Release of mediators from infiltrating inflammatory cells in the airway mucosa has been proposed to contribute directly or indirectly to changes in airway structure and function. The airway smooth muscle, which has been regarded as a contractile component of the airways responding to various mediators and neurotransmitters, has recently been recognised as a rich source of pro-inflammatory cytokines, chemokines and growth factors. In this review, we discuss the role of airway smooth muscle cells in the regulation and perpetuation of airway inflammation that contribute to the pathogenesis of asthma.

Effect of long-term maternal smoking on the offspring’s lung health

“…This is in keeping with increased protein levels of the proinflammatory cytokines IL-1␤ and TNF-␣, both of which are the downstream targets of NF-B. It has been reported that chronic production of IL-1␤ can lead to pulmonary inflammation, emphysema, airway remodeling, and bronchial hyperreactivity, which are the main features of asthma and COPD (23,31,35). Therefore, maternal smoking during pregnancy may increase the risk of chronic inflammatory conditions in offspring lungs, making them more susceptible to certain pulmonary disorders such as COPD in adulthood, which requires further investigation.…”

The impact of vitamin D on asthmatic human airway smooth muscle

“…Activation of the TSLP receptor on HASM cells led to enhanced secretion of IL-6, IL-8/CXCL8 and eotaxin/CCL11 [41]. These mediators are well known for the roles in promoting mucus hypersecretion (IL-6), recruiting inflammatory cells to the airways (IL-8 and CCL11) as well as promoting differentiation of lymphocytes (IL-6) [42]. …”

Rho-Kinase as a Drug Target for the Treatment of Airway Hyperresponsiveness in Asthma

“…These cells are potent producers of cytokines, chemokines and extracellular matrix proteins [34][35][36][37]. Moreover, passively sensitized airway smooth muscle cells [38], and asthmatic fibroblasts [39] produce more extracellular matrix when compared to cells obtained from healthy controls and thus, exhibit a profibrotic state.…”