AIMS: 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. METHODS AND 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. CONCLUSION: 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.
AIMS: 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. METHODS AND 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. CONCLUSION: 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: Jennifer E Ho; Wei-Yu Chen; Ming-Huei Chen; Martin G Larson; Elizabeth L McCabe; Susan Cheng; Anahita Ghorbani; Erin Coglianese; Valur Emilsson; Andrew D Johnson; Stefan Walter; Nora Franceschini; Christopher J O'Donnell; Abbas Dehghan; Chen Lu; Daniel Levy; Christopher Newton-Cheh; Honghuang Lin; Janine F Felix; Eric R Schreiter; Ramachandran S Vasan; James L Januzzi; Richard T Lee; Thomas J Wang Journal: J Clin Invest Date: 2013-09-03 Impact factor: 14.808
Authors: Hemanth Ramaprakash; Takehiko Shibata; Karen E Duffy; Ugur B Ismailoglu; Rachel M Bredernitz; Ana Paula Moreira; Ana L Coelho; Anuk M Das; Natalie Fursov; Geoffrey L Chupp; Cory M Hogaboam Journal: Am J Pathol Date: 2011-05-14 Impact factor: 4.307
Authors: Dipal M Patel; Heather Thiessen-Philbrook; Jeremiah R Brown; Eric McArthur; Dennis G Moledina; Sherry G Mansour; Michael G Shlipak; Jay L Koyner; Peter Kavsak; Richard P Whitlock; Allen D Everett; David J Malenka; Amit X Garg; Steven G Coca; Chirag R Parikh Journal: Am Heart J Date: 2019-12-03 Impact factor: 4.749