{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["14(4)"],"submitter":["Kim SK"],"pubmed_abstract":["Carbon monoxide (CO) can act as an anti-inflammatory effector in mouse models of lung injury and disease, through the downregulation of pro-inflammatory cytokines production, though the underlying mechanisms remain unclear. The nucleotide-binding oligomerization domain-, leucine-rich region-, and pyrin domain-containing-3 (NLRP3) inflammasome is a protein complex that regulates the maturation and secretion of pro-inflammatory cytokines, including interleukin-1β (IL-1β). In this report, we show that the CO-releasing molecule (CORM-2) can stimulate the expression of pyrin, a negative regulator of the NLRP3 inflammasome. CORM-2 increased the transcription of pyrin in the human leukemic cell line (THP-1) in the absence and presence of lipopolysaccharide (LPS). In THP-1 cells, CORM-2 treatment dose-dependently reduced the activation of caspase-1 and the secretion of IL-1β, and increased the levels of IL-10, in response to LPS and adenosine 5'-triphosphate (ATP), an NLRP3 inflammasome activation model. Genetic interference of IL-10 by small interfering RNA (siRNA) reduced the effectiveness of CORM-2 in inhibiting IL-1β production and in inducing pyrin expression. Genetic interference of pyrin by siRNA increased IL-1β production in response to LPS and ATP, and reversed CORM-2-dependent inhibition of caspase-1 activation. CO inhalation (250 ppm) in vivo increased the expression of pyrin and IL-10 in lung and spleen, and decreased the levels of IL-1β induced by LPS. Consistent with the induction of pyrin and IL-10, and the downregulation of lung IL-1β production, CO provided protection in a model of acute lung injury induced by intranasal LPS administration. These results provide a novel mechanism underlying the anti-inflammatory effects of CO, involving the IL-10-dependent upregulation of pyrin expression."],"journal":["Cellular & molecular immunology"],"pagination":["349-359"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5380940"],"repository":["biostudies-literature"],"pubmed_title":["Carbon monoxide decreases interleukin-1β levels in the lung through the induction of pyrin."],"pmcid":["PMC5380940"],"pubmed_authors":["Ryter SW","Ryu J","Cho GJ","Chung HT","Chen Y","Kim SK","Joe Y","Lee JH"],"additional_accession":[]},"is_claimable":false,"name":"Carbon monoxide decreases interleukin-1β levels in the lung through the induction of pyrin.","description":"Carbon monoxide (CO) can act as an anti-inflammatory effector in mouse models of lung injury and disease, through the downregulation of pro-inflammatory cytokines production, though the underlying mechanisms remain unclear. The nucleotide-binding oligomerization domain-, leucine-rich region-, and pyrin domain-containing-3 (NLRP3) inflammasome is a protein complex that regulates the maturation and secretion of pro-inflammatory cytokines, including interleukin-1β (IL-1β). In this report, we show that the CO-releasing molecule (CORM-2) can stimulate the expression of pyrin, a negative regulator of the NLRP3 inflammasome. CORM-2 increased the transcription of pyrin in the human leukemic cell line (THP-1) in the absence and presence of lipopolysaccharide (LPS). In THP-1 cells, CORM-2 treatment dose-dependently reduced the activation of caspase-1 and the secretion of IL-1β, and increased the levels of IL-10, in response to LPS and adenosine 5'-triphosphate (ATP), an NLRP3 inflammasome activation model. Genetic interference of IL-10 by small interfering RNA (siRNA) reduced the effectiveness of CORM-2 in inhibiting IL-1β production and in inducing pyrin expression. Genetic interference of pyrin by siRNA increased IL-1β production in response to LPS and ATP, and reversed CORM-2-dependent inhibition of caspase-1 activation. CO inhalation (250 ppm) in vivo increased the expression of pyrin and IL-10 in lung and spleen, and decreased the levels of IL-1β induced by LPS. Consistent with the induction of pyrin and IL-10, and the downregulation of lung IL-1β production, CO provided protection in a model of acute lung injury induced by intranasal LPS administration. These results provide a novel mechanism underlying the anti-inflammatory effects of CO, involving the IL-10-dependent upregulation of pyrin expression.","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Apr","modification":"2022-02-09T09:27:04.908Z","creation":"2019-03-27T02:40:24Z"},"accession":"S-EPMC5380940","cross_references":{"pubmed":["26435068"],"doi":["10.1038/cmi.2015.79"]}}