title: Pentraxin 3 (PTX3) expression in allergic asthmatic airways: role in airway smooth muscle migration and chemokine production.
abstract: BACKGROUND
  Pentraxin 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.
  
  
  OBJECTIVE
  We 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 (3)H-thymidine incorporation, cell count and Boyden chamber assays.
  
  
  RESULTS
  PTX3 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Zhang
authors.forename: Lianyu
authors.initials: L
authors.lastname: Shan
authors.forename: Latifa
authors.initials: L
authors.lastname: Koussih
authors.forename: Naresh Singh
authors.initials: NS
authors.lastname: Redhu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Halayko
authors.forename: Jamila
authors.initials: J
authors.lastname: Chakir
authors.forename: Abdelilah S
authors.initials: AS
authors.lastname: Gounni
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000378:metabolism*; D001706:Biopsy; D001980:Bronchi / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002097:C-Reactive Protein / Q000276:immunology / Q000378:metabolism*; D054413:Chemokine CCL11 / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis*; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D000683:Serum Amyloid P-Component / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D055815:Young Adult; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D054413:Chemokine CCL11; D018925:Chemokines; D016207:Cytokines; D016222:Fibroblast Growth Factor 2; D000683:Serum Amyloid P-Component; D000099153:Pentraxins