Search

Asthma is a chronic inflammatory process that leads to airway narrowing, causing breath loss followed by spasms, wheezing, and shortness of breath. Within the asthmatic lungs, interaction among various immune cells and structural cells plays a significant role in orchestrating an inflammatory response in which eosinophils hold central importance. In these settings, allergens or other environmental exposures commonly drive the immune response to recruit eosinophils to the airways. The appearance of eosinophils in the airways indicates a dynamic interplay of various cell types within lung tissue and does not represent a passive effect of inflammation. The cellular cross-talk causes the persistence of eosinophilic inflammation, and if left untreated, it results in long-term damage to the airway structure and function. Further exacerbation of the condition occurs because of this. We discuss how this complex interplay of eosinophils, immune, and structural cells within the airway microenvironment leads to the distinct pathophysiological features in asthma, the variability in disease severity, and the response to biological treatments. [ABSTRACT FROM AUTHOR]

The current therapeutic strategy used in immune-mediated inflammatory diseases (IMIDs) primarily targets immune cells or associated-pathways. However, recent evidence suggests that the microenvironment modulates immune cell development and responses. During inflammation, structural cells acquire a pathogenetic phenotype and the interactions with immune cells are often greatly modified. Understanding the importance of these tissue-specific interactions may allow to explain why some biologics are effective in some IMIDs but not in others. The differential effects of interleukin (IL)-17 A, IL-17F and IL-23 in joint versus skin inflammation depends on structural cell heterogeneity. In addition, the sometimes opposite effects of immune/structural cell interactions on the production of these cytokines illustrate the importance of these cells in chronic inflammation, using the examples of rheumatoid arthritis, psoriasis and spondyloarthritis. This review describes these concepts, shows their interests through clinical observations, and finally discusses strategies to optimize therapeutic strategies. • Immune-structural cell interactions contribute to disease induction and chronicity. • Effects of IL-17A, IL-17F and IL-23 vary according to the affected tissue. • Immune-structural cells interactions modulate IL-17A, IL-17F and IL-23 production. • Key differences are observed with cells from joint versus skin tissue. • Such differences help to understand why their inhibition is useful in some diseases but not in others. [ABSTRACT FROM AUTHOR]

Urban trees face a litany of challenges from heat and air pollution through to undesirable soil conditions that hinder root development and negatively impact on overall growth and stability. Engineered soils have been designed to improve root colonisation zones and enhance soil volumes for trees with limited rooting space. In this study, force was applied to determine trunk resistance using a pulley and winch under regular and heavily irrigated soils to understand the stability of four tree species (Peltophorum pterocarpum, Samanea saman, Pouteria obovata and Calophyllum inophyllum) growing in different soil blends after 5 years of growth. Previous research has confirmed that these soils are beneficial to growth. Trees grown in skeletal soils (stone and gravel soil blends) were significantly more stable than trees planted in structural cells and compacted soils. Less force was required to deflect trees in near-saturated soils as compared to those in soils with less moisture. Samanea saman was found to be most stable across the various species and was especially so in the skeletal blends. The relationship between tree stability and engineered blends has received limited scientific scrutiny and the conclusions here provide evidence that some species are more susceptible to uprooting because of limited rooting space and that stability might be enhanced using engineered blends. [ABSTRACT FROM AUTHOR]

Human airway smooth muscle (ASM) plays an immunomodulatory role in asthma. Recently, IL-17A has become of increasing interest in asthma, being found at elevated levels in asthmatic airways and emerging as playing an important role in airway neutrophilia. IL-17A predominantly exerts its neutrophil orchestrating role indirectly via the induction of cytokines by resident airway structural cells. Here, we perform an in vitro study to show that although IL-17A did not induce secretion of the CXC chemokine IL-8 from ASM cells, IL-17A significantly potentiates TNF-α-induced IL-8 protein secretion and gene expression in a concentration- and time-dependent manner (P < 0.05). Levels of IL-8 protein produced after 24 h of incubation with TNF-α were enhanced 2.7-fold in the presence of IL-17A, and conditioned media significantly enhanced neutrophil chemotaxis in vitro. As IL-17A had no effect on the activity of NF-κB, a key transcriptional regulator of IL-8 gene expression, we then examined whether IL-17A acts at the posttranscriptional level. We found that IL-17A significantly augmented TNF-α-induced IL-8 mRNA stability. Interestingly, this enhanced stability occurred via a p38 MAPK-dependent pathway. The decay of IL-8 mRNA transcripts proceeded at a significantly faster rate when cells were pretreated with the p38 MAPK inhibitor SB-203580 (-0.05763 ± 0.01964, t1/2 = 12.0 h), compared with vehicle (-0.0 1030 ± 0.007963, t1/2 = 67.3 h) [results are expressed as decay constant (means ± SE) and half-life (t1/2 in h): P < 0.051. Collectively, these results demonstrate that IL-17A amplifies the synthetic function of ASM cells, acting via a p38 MAPK-dependent posttranscriptional pathway to augment TNF-α-induced secretion of the potent neutrophil chemoattractant IL-8 from ASM cells. [ABSTRACT FROM AUTHOR]

Asthma is a chronic inflammatory and allergic disease that is mainly characterized by reversible airway obstruction and bronchial hyperresponsiveness. The incidence of asthma is increasing with more than 350 million people worldwide are affected. Up to now, there is no therapeutic option for asthma and most of the prescribed drugs aim to ameliorate the symptoms of the disease especially during the acute exacerbations after trigger exposure. Asthma is a heterogonous disease that involves interactions between inflammatory mediators and cellular components within the disease microenvironment including inflammatory and structural cells. Cysteinyl leukotrienes (cys-LTs) are inflammatory lipid mediators that have potent roles in asthma pathogenesis. CysLTs consisting of LTC 4 , LTD 4 , and LTE 4 are mainly secreted by leukocytes and act through three main G-protein coupled receptors (CysLT 1 R, CysLT 2 R, and CysLT 3 R). LTD 4 is the most potent bronchoconstrictor which gives it the priority to be discussed in detail in this review. LTD 4 binds with high affinity to CysLT 1 R and many studies showed that using CysLT 1 R antagonists such as montelukast has a beneficial effect for asthmatics especially in corticosteroid refractory cases. Since asthma is a heterogeneous inflammatory disease of many cell types involved in the disease pathogenies and LTD 4 has a special role in inflammation and bronchoconstriction, this review highlights the role of LTD 4 on each cellular component in asthma and the benefits of using CysLT 1 R antagonists in ameliorating LTD 4 -induced effects. Unlabelled Image [ABSTRACT FROM AUTHOR]