title: TNF up-regulates Pentraxin3 expression in human airway smooth muscle cells via JNK and ERK1/2 MAPK pathways.
abstract: BACKGROUND
  Long 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.
  
  
  METHODS
  HASMC 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.
  
  
  RESULTS
  PTX3 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Immunology, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB Canada ; Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB Canada ; Universite de Saint Boniface, 200 Avenue de la cathedrale, Winnipeg, MB Canada.
authors.forename: Latifa
authors.initials: L
authors.lastname: Koussih
authors.affiliation: Department of Immunology, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB Canada.
authors.forename: Lianyu
authors.initials: L
authors.lastname: Shan
authors.affiliation: Department of Immunology, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB Canada ; Physiology and Physiopathology, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Halayko
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ben-Kuen
authors.initials: BK
authors.lastname: Chen
authors.affiliation: Department of Immunology, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB Canada.
authors.forename: Abdelilah S
authors.initials: AS
authors.lastname: Gounni
keywords: Airway smooth muscle cells; Pentraxin-3; Signaling; TNF