Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endotoxin and proinflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNFalpha) induce a state of GH resistance. A new family of suppressors of cytokine signaling (SOCS), induced by cytokines activating the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, has been recently identified as a negative feedback loop of intracellular signaling. Overexpression of some SOCS (SOCS-3, CIS, and SOCS-2) has been reported to inhibit the JAK-STAT pathway stimulated by GH. To assess the possible role of these three SOCS proteins in the GH resistance induced by endotoxin and cytokines, we investigated the regulation of their gene expression by endotoxin and GH in rat liver and by proinflammatory cytokines and GH in primary culture hepatocytes. Both GH and lipopolysaccharide induced the three SOCS messenger RNAs (mRNAs) in vivo. In vitro, GH also increased the liver mRNAs encoding SOCS-2, SOCS-3, and CIS. Although IL-1/beta and TNFalpha alone induced only weakly the expression of SOCS-3 and CIS, these cytokines strongly potentiated the induction of these two SOCS by GH. In contrast, IL-6 alone markedly induced SOCS-3 mRNA, but did not potentiate the GH action on SOCS-3 and CIS mRNAs. The GH induction of SOCS-2 was not potentiated by any of these cytokines. Considering the ability of these SOCS to inhibit the JAK-STAT pathway induced by GH, these results suggest that the overexpression of SOCS-3 and CIS mRNAs induced by IL-1beta and TNFalpha or by endotoxin in vivo may play a role in the GH resistance induced by sepsis.
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PMID:Potentiation of growth hormone-induced liver suppressors of cytokine signaling messenger ribonucleic acid by cytokines. 1101 23

GH treatment during critical illness and sepsis may increase mortality. A family of negative regulators of cytokine signalling, the suppressors of cytokine signalling (SOCS), have been characterised. SOCS provide a mechanism for cross-talk between the cytokine receptors, including GH. Here, we have investigated the impact of nutrition and GH treatment on GH receptor, SOCS1, SOCS-2, SOCS-3 and cytokine-inducible SH2-containing protein (CIS) hepatic mRNA expression in a rat model of sepsis, caecal ligation and puncture (CLP). Four groups of rats were studied: control (food given ad libitum, n=7), CLP only (n=8), CLP and total parenteral nutrition (TPN) (n=9), and CLP, TPN and GH (n=10). CLP rats underwent surgery and 18 h later received saline or TPN or TPN+GH for 6 h before they were killed. Serum IGF-I levels were lower in all CLP groups (P<0.001). The combination of TPN and GH treatment increased IGF-I levels compared with the saline-treated CLP rats (P<0.01), but IGF-I levels remained lower than control animals (P<0.001). GH receptor and GH-binding protein expression in liver was reduced in animals subjected to CLP and was unaffected by nutrition or GH treatment. Hepatic SOCS-1 was detectable in normal rats, induced in all CLP animals but was unaffected by nutrition and GH. Hepatic SOCS-2 expression was difficult to detect in normal and CLP rats but was greatly induced in CLP rats treated with GH. Hepatic SOCS-3 expression was only just detectable in the control group but was elevated in all CLP groups and unaffected by nutrition and GH. Hepatic CIS expression was difficult to detect in normal rats, was not induced by CLP but was induced by both nutrition and GH. In conclusion, CLP induced low IGF-I levels associated with increased expression of SOCS-1 and SOCS-3, both of which are known to inhibit GH receptor signalling. GH induced SOCS-2 and CIS in the CLP rat despite resistance with respect to IGF-I generation, and parenteral feeding induced CIS in the CLP rat. Thus, there is potential for a complex interaction between GH and cytokine signalling at the level of SOCS expression whereby the inflammatory response may alter GH signalling and GH may influence the inflammatory response.
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PMID:Differential expression of suppressors of cytokine signalling genes in response to nutrition and growth hormone in the septic rat. 1131 57

Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathways and key physiological regulators of both innate and adaptive immune systems in vertebrates. In present study, we provided the initial characterization of SOCS-2 homologue from the mollusk abalone Haliotis discus discus as a member of invertebrate SOCS-2. The disk abalone SOCS-2 cDNA (AbSOCS-2) contains 1700-bp full length with 771-bp coding sequence, which codes 257 amino acids protein. Based on the sequence analysis results, AbSOCS-2 showed characteristic SH2 domain and SOCS box similar to vertebrate SOCS counterparts. Additionally, 3' UTR of the AbSOCS-2 contained two RNA instability motifs (ATTTA). Quantitative real-time PCR expression results showed that AbSOCS-2 was constitutively expressed in all examined tissues of healthy abalone showing tissue specific variation. AbSOCS-2 mRNA expression was induced significantly (p < 0.05) by bacteria mixture containing Vibrio alginolyticus, Vibrio parahemolyticus, and Listeria monocytogenes in abalone gill at 3 h post-induction (p.i.). Furthermore, AbSOC-2 mRNA was significantly (p < 0.05) induced by viral haemorrhagic septicemia virus (VHSV) and lipopolysaccharide (LPS) treatments in abalone gill. Therefore, discovery and expression analysis of abalone SOCS-2 gene would provide evolutional relationship of SOCS family members and immune defense responses against bacteria, virus and LPS like immune modulators.
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PMID:Suppressor of cytokine signaling 2 (SOCS-2) homologue in disk abalone: cloning, sequence characterization and expression analysis. 1934 Sep 53