Research Upregulation of CD23 (FcεRII) Expression in Human Airway Smooth Muscle Cells (huASMC) in Response to IL-4, GM-CSF, and IL-4/GM-CSF

Abstract

BackgroundAirway smooth muscle cells play a key role in remodeling that contributes to airway hyperreactivity. Airway smooth muscle remodeling includes hypertrophy and hyperplasia. It has been previously shown that the expression of CD23 on ASMC in rabbits can be induced by the IgE component of the atopic serum. We examined if other components of atopic serum are capable of inducing CD23 expression independent of IgE.MethodsSerum starved huASMC were stimulated with either IL-4, GM-CSF, IL-13, IL-5, PGD2, LTD4, tryptase or a combination of IL-4, IL-5, IL-13 each with GM-CSF for a period of 24 h. CD23 expression was analyzed by flow cytometry, western blot, and indirect immunofluorescence.ResultsThe CD23 protein expression was upregulated in huASMC in response to IL-4, GM-CSF, and IL-4/GM-CSF. The percentage of cells with increased fluorescence intensity above the control was 25.1 ± 4.2% (IL-4), 15.6 ± 2.7% (GM-CSF) and 32.9 ± 13.9% (IL-4/GMCSF combination)(n = 3). The protein content of IL-4/GMCSF stimulated cells was significantly elevated. Expression of CD23 in response to IL-4, GM-CSF, IL-4/GM-CSF was accompanied by changes in cell morphology including depolymerization of isoactin fibers, cell spreading, and membrane ruffling. Western blot revealed abundant expression of the IL-4Rα and a low level expression of IL-2Rγc in huASMC. Stimulation with IL-4 resulted in the phosphorylation of STAT-6 and an increase in the expression of the IL-2Rγc.ConclusionCD23 on huASMC is upregulated by IL-4, GM-CSF, and IL-4/GM-CSF. The expression of CD23 is accompanied by an increase in cell volume and an increase in protein content per cell, suggesting hypertrophy. Upregulation of CD23 by IL-4/GM-CSF results in phenotypic changes in huASMC that could play a role in cell migration or a change in the synthetic function of the cells. Upregulation of CD23 in huASMC by IL-4 and GM-CSF can contribute to changes in huASMC and may provide an avenue for new therapeutic options in asthma targeting ASMC.

Urtica dioica attenuates ovalbumin-induced inflammation and lipid peroxidation of lung tissues in rat asthma model

“…It is also the primary mediator of immunoglobulin class switching (Ig) that induces the human expression of low affinity receptor, FcɛRII, for IgE (Belleau et al. 2005 ). In addition, the increased levels of these cytokines stimulate the profibrotic transformation of TGF-β, which is expressed in various lung cells such as alveolar macrophages, fibroblasts and endothelial cells by inducing increased accumulation of the extracellular matrix and thickening of the inter- alveolar septa (Halwani et al.…”

The Role of IgE-Receptors in IgE-Dependent Airway Smooth Muscle Cell Remodelling

“…The thickening of the airway wall in asthma is largely caused by hypertrophy and hyperplasia of airway smooth muscle cells (ASMC) which express and respond to the Igε−RI and Igε−RII [12]–[14].…”

Evolution of our view on the IgE molecule role in bronchial asthma and the clinical effect of its modulation by omalizumab: Where do we stand today?

“…We have already known for some time that activated mastocytes can also affect the long-term remodelling processes through their interaction with smooth muscle cells. 48 As a new, relatively recent development, expression of both receptor types for IgE has been discovered on the surface of smooth muscle cells in the airways 49 , 50 and a direct correlation was found between IgE levels and proliferation of the smooth muscle cells and type I, III, VII collagen and fibronectin production 51 (see Figure 5 , part 5). Experimental evidence has also been provided that this effect does not depend on the interaction IgE with an allergen, and furthermore, it can be affected by therapy consisting of the administration of a blocking antibody – omalizumab.…”