title: Primary sources and immunological prerequisites for sST2 secretion in humans.
abstract: OBJECTIVE
  Serum levels of the soluble growth stimulation gene-2 (sST2) are elevated in heart and pulmonary diseases. However, the relationship of the sST2/interleukin (IL)-33 axis and its triggers as well as its organ distribution is still not known. This study was thus designed to investigate the cellular origin and regulation of sST2 and IL-33 in vitro and in vivo.
  
  
  RESULTS
  sST2 and IL-33 gene expression and protein secretion were analysed in pooled organ-specific cDNAs and in primary cell cultures, respectively, by RT-PCR and ELISA technology. The strongest sST2 mRNA expression was detected in heart and lung tissues, which correlated with spontaneous secretion of sST2 protein in vitro. The inflammatory cytokines IL-1alpha, IL-1beta, and tumour necrosis factor alpha as well as supernatants of lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells led to an enhanced secretion of sST2 in cultured cardiac myocytes and lung alveolar epithelial cells. These cytokines enhanced sST2 secretion via an NFkappaB-dependent mechanism. In addition, LPS stimulation in humans in vivo induced a short-term inflammatory response that was followed by a massive enhancement of sST2 secretion.
  
  
  CONCLUSIONS
  These results identify the primary sources and inflammatory triggers for the enhancement of sST2 secretion and demonstrate a relationship between inflammation and the secretion of a bioactive member of the IL-1R family, both in vitro and in vivo.
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Mildner
authors.forename: Angela
authors.initials: A
authors.lastname: Storka
authors.forename: Michael
authors.initials: M
authors.lastname: Lichtenauer
authors.forename: Veronika
authors.initials: V
authors.lastname: Mlitz
authors.forename: Minoo
authors.initials: M
authors.lastname: Ghannadan
authors.forename: Konrad
authors.initials: K
authors.lastname: Hoetzenecker
authors.forename: Stefanie
authors.initials: S
authors.lastname: Nickl
authors.forename: Balazs
authors.initials: B
authors.lastname: Dome
authors.forename: Erwin
authors.initials: E
authors.lastname: Tschachler
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Ankersmit
mesh_terms: D056704:Adaptive Immunity; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053582:Interleukin-1alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D018836:Inflammation Mediators; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D000067596:Interleukin-33; D007378:Interleukins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha