Pentraxin 3 (PTX3) Expression in Allergic Asthmatic Airways: Role in Airway Smooth Muscle Migration and Chemokine Production

Abstract

BackgroundPentraxin 3 (PTX3) is a soluble pattern recognition receptor with non-redundant functions in inflammation and innate immunity. PTX3 is produced by immune and structural cells. However, very little is known about the expression of PTX3 and its role in allergic asthma.Objectives and MethodsWe sought to determine the PTX3 expression in asthmatic airways and its function in human airway smooth muscle cells (HASMC). In vivo PTX3 expression in bronchial biopsies of mild, moderate and severe asthmatics was analyzed by immunohistochemistry. PTX3 mRNA and protein were measured by real-time RT-PCR and ELISA, respectively. Proliferation and migration were examined using 3H-thymidine incorporation, cell count and Boyden chamber assays.ResultsPTX3 immunoreactivity was increased in bronchial tissues of allergic asthmatics compared to healthy controls, and mainly localized in the smooth muscle bundle. PTX3 protein was expressed constitutively by HASMC and was significantly up-regulated by TNF, and IL-1β but not by Th2 (IL-4, IL-9, IL-13), Th1 (IFN-γ), or Th-17 (IL-17) cytokines. In vitro, HASMC released significantly higher levels of PTX3 at the baseline and upon TNF stimulation compared to airway epithelial cells (EC). Moreover, PTX3 induced CCL11/eotaxin-1 release whilst inhibited the fibroblast growth factor-2 (FGF-2)-driven HASMC chemotactic activity.ConclusionsOur data provide the first evidence that PTX3 expression is increased in asthmatic airways. HASMC can both produce and respond to PTX3. PTX3 is a potent inhibitor of HASMC migration induced by FGF-2 and can upregulate CCL11/eotaxin-1 release. These results raise the possibility that PTX3 may play a dual role in allergic asthma.

Activin-A is overexpressed in severe asthma and is implicated in angiogenic processes

“…Predominance of expression of a certain cytokine by the bronchial epithelium does not preclude a pathogenic role for the corresponding factor in other cell types and processes. In fact, several mediators involved in asthma pathophysiology, such as TGF-β [49,50], osteopontin [38,51], pentraxin-3 [52] and resistin-like molecule-β [53] are prominently expressed in the bronchial epithelium and exert effects on subepithelial cells. Interestingly, and in agreement with other studies, our findings demonstrated that activin-A is also localised in the nucleus of subepithelial cells in the bronchial mucosa, possibly reflecting other, unidentified roles for this cytokine in gene regulation [54,55].…”

Sputum pentraxin 3 as a candidate to assess airway inflammation and remodeling in childhood asthma

“…[12] Furthermore, increased PTX3 protein production in bronchial tissue, mainly in airway smooth muscle cells (AMSCs), was initially reported in adult asthma patients. [14] An in vitro study reported that the release of PTX3 from human AMSCs was stimulated by proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor (TNF)], and PTX3 enhanced the release of C-C motif chemokine ligand 11 (CCL11)/eotaxin-1, which is an important chemokine in eosinophilic airway inflammation and remodeling. It is inferred that PTX3 may be involved in the pathogenesis of asthma, with the induction of CCL11/eotaxin-1 expression in inflammatory conditions affecting structural alterations in asthmatic airways.…”

“…[9] An association between PTX3 and chronic airway inflammatory diseases has been also discovered. [10–14] However, the precise role of PTX3 in chronic lung inflammation has not been established, particularly in children.…”

IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle

“…A second notable gene is PTX, which encodes innate immunity protein pentraxin 3. Elevated levels of pentraxin 3 protein have been measured in the bronchial tissues of allergic asthmatic subjects and are primarily detected in ASM cells (75). Pentraxin 3 levels also become elevated in subjects with ARDS within 24 h of diagnosis, presumably as an activator of the local innate immune system in the lung (3).…”