Abstract
BackgroundLong pentraxin 3 (PTX3) is a novel candidate marker for inflammation in many chronic diseases. As a soluble pattern recognition receptor, PTX3 is involved in amplification of inflammatory reactions and regulation of innate immunity. Previously, we demonstrate that human airway smooth muscle cells (HASMC) express constitutively PTX3 and upon TNF stimulation. However, very little is known about the mechanism governing its expression in HASMC. We sought to investigate the mechanism governing TNF induced PTX3 expression in primary HASMC.MethodsHASMC were stimulated with TNF in the presence of transcriptional inhibitor actinomycin D (ActD) or MAPKs pharmacological inhibitors. PTX3 mRNA and protein expression were analyzed by Real-time RT-PCR and ELISA, respectively. PTX3 promoter activity was determined using luciferase assay.ResultsPTX3 mRNA and protein are expressed constitutively by HASMC and significantly up-regulated by TNF. TNF-induced PTX3 mRNA and protein release in HASMC were inhibited by transcriptional inhibitor actinomycin D. TNF induced significantly PTX3 promoter activation in HASMC. MAPK JNK and ERK1/2 specific inhibitors (SP600125 and UO126), but not p38, significantly down regulates TNF induced PTX3 promoter activity and protein release in HASMC. Finally, TNF mediated PTX3 promoter activity in HASMC was abolished upon mutation of NF-κβ and AP1 binding sites.ConclusionsOur data suggest that TNF induced PTX3 in HASMC at least via a transcriptional mechanism that involved MAPK (JNK and ERK1/2), NF-κβ and AP1 pathways. These results rise the possibility that HASMC derived PTX3 may participate in immune regulation in the airways.
Highlights
Long pentraxin 3 (PTX3) is a novel candidate marker for inflammation in many chronic diseases
to asthmaTumor necrosis factor (TNF) induced PTX3 expression in human airway smooth muscle cells (HASMC) via a transcriptional mechanism We first confirmed in different primary HASMC that TNF stimulation induces PTX3 mRNA expression
Since TNF is one of the critical proinflammatory effector cytokines in asthma, and has been shown to induce multiple inflammatory genes in HASMC [21, 22], we further characterized the kinetic of TNF induced PTX3 mRNA expression using quantitative real-time RT-PCR
Summary
Long pentraxin 3 (PTX3) is a novel candidate marker for inflammation in many chronic diseases. We demonstrate that human airway smooth muscle cells (HASMC) express constitutively PTX3 and upon TNF stimulation. Very little is known about the mechanism governing its expression in HASMC. We sought to investigate the mechanism governing TNF induced PTX3 expression in primary HASMC. Asthma is a major cause of morbidity and mortality worldwide. It is a chronic inflammatory condition of the airways characterized by bronchial hyperresponsiveness, infiltration of inflammatory cells, and airway remodeling [1]. Airway smooth muscle cells (ASMC) are one of the tissue-forming lung cells that have recently gained appreciation as one of the major contributors to asthma. Tumor necrosis factor (TNF) is a well characterized proinflammatory cytokine that plays a central role in asthma pathogenesis through direct immunomodulatory actions on ASMC [4]. Cumulative evidence suggests that the PTX3 could serve as a useful new serological marker, rapidly reflecting tissue inflammation and damage under diverse clinical conditions [8]
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