SOCS1 is a negative regulator of metabolic reprogramming during sepsis

Piñeros, Annie R.; Glosson-Byers, Nicole L.; Brandt, Stephanie; Wang, Soujuan; Wong, Hector R.; Sturgeon, Sarah; McCarthy, Brian P.; Territo, Paul R.; Alves-Filho, José C.; Serezani, C. Henrique

doi:10.1172/jci.insight.92530

Cited by 35 publications

(30 citation statements)

References 91 publications

(123 reference statements)

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“…To prevent excessive and harmful inflammatory responses, these inflammatory signaling pathways are negatively controlled by multiple mechanisms. So far, many negative regulators of TLR4 signaling (Tollip and SOCS1) and NOD signaling (ERBB2IP and centaurin β1) have been identified and characterized [ 50 , 51 ]. The current results showed that the piglets challenged with LPS had decreased mRNA expression of Tollip both in jejunum and ileum, as well as ERBB2IP and centaurin β1 in ileum, which is in agreement with the report of Wang et al [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Glycine Relieves Intestinal Injury by Maintaining mTOR Signaling and Suppressing AMPK, TLR4, and NOD Signaling in Weaned Piglets after Lipopolysaccharide Challenge

Wang

et al. 2018

IJMS

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This study was conducted to envaluate whether glycine could alleviate Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury by regulating intestinal epithelial energy status, protein synthesis, and inflammatory response via AMPK, mTOR, TLR4, and NOD signaling pathways. A total of 24 weanling piglets were randomly allotted to 1 of 4 treatments: (1) non-challenged control; (2) LPS-challenged control; (3) LPS + 1% glycine; (4) LPS + 2% glycine. After 28 days feeding, piglets were injected intraperitoneally with saline or LPS. The pigs were slaughtered and intestinal samples were collected at 4 h postinjection. The mRNA expression of key genes in these signaling pathways was measured by real-time PCR. The protein abundance was measured by Western blot analysis. Supplementation with glycine increased jejunal villus height/crypt depth ratio. Glycine also increased the jejunal and ileal protein content, RNA/DNA ratio, and jejunal protein/DNA ratio. The activities of citroyl synthetase in ileum, and α-ketoglutarate dehydrogenase complex in jejunum, were increased in the piglets fed diets supplemented with glycine. In addition, glycine decreased the jejunal and ileal phosphorylation of AMPKα, and increased ileal phosphorylation of mTOR. Furthermore, glycine downregulated the mRNA expression of key genes in inflammatory signaling. Meanwhile, glycine increased the mRNA expression of negative regulators of inflammatory signaling. These results indicate that glycine supplementation could improve energy status and protein synthesis by regulating AMPK and mTOR signaling pathways, and relieve inflammation by inhibiting of TLR4 and NOD signaling pathways to alleviate intestinal injury in LPS-challenged piglets.

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Section: Discussionmentioning

confidence: 99%

Glycine Relieves Intestinal Injury by Maintaining mTOR Signaling and Suppressing AMPK, TLR4, and NOD Signaling in Weaned Piglets after Lipopolysaccharide Challenge

Wang

et al. 2018

IJMS

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“…In the present study, various genes involved in the Jak-STAT signaling pathway had increased expression in susceptible birds than in non-infected controls, including IL10RA , IL10RB , BCL2-like 1 ( BCL2L1 ) and suppressor of cytokine signaling 1 ( SOCS1 ). BCL2L1 is one the family of Bcl-2 proteins with important roles in the regulation of mitochondrial pathway of apoptosis ( Cory and Adams, 2002 ) and SOCS1 is a negative regulator of LPS-induced macrophage activation ( Kinjyo et al, 2002 ; Alvarez et al, 2017 ). Interestingly, three overlapping elements were found in Jak-STAT and cytokine-cytokine receptor interaction pathways in susceptible birds, both in S vs. C and S vs. R comparisons ( Figure 5 ).…”

Section: Discussionmentioning

confidence: 99%

Messenger RNA Sequencing and Pathway Analysis Provide Novel Insights Into the Susceptibility to Salmonella enteritidis Infection in Chickens

Fan

Everaert

et al. 2018

Front. Genet.

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Salmonella enteritidis (SE) is a foodborne pathogen that negatively affects both animal and human health. Controlling poultry SE infection will have great practical significance for human public health, as poultry are considered to be important sources and carriers of the disease. In this study, the splenic transcriptomes of challenged-susceptible (S), challenged-resistant (R) and non-challenged (C) chicks (3-days old, specific-pathogen-free White Leghorn) were characterized in order to identify the immune-related gene markers and pathways. A total of 934 significant differentially expressed genes (DEGs) were identified in comparisons among the C, R and S birds. First reported here, the DEGs involved in the Forkhead box O (FoxO) signaling pathway, especially FoxO3, were identified as potential markers for host resistance to SE infection. The challenged-susceptible birds exhibited strong activation of the FoxO signaling pathway, which may be a major defect causing immune cell apoptosis as part of SE-induced pathology; these S birds also showed weak activation of mitogen-activated protein kinase (MAPK)-related genes, contrasting with strong splenic activation in the R birds. Interestingly, suppression of several pathways in the immune response against Salmonella, including cytokine-cytokine receptor interaction and Jak-STAT, was only found in S birds and there was evidence of cross-talk among these pathways, perhaps contributing to susceptibility to Salmonella infection. These findings will help facilitate understanding resistance and susceptibility to SE infection in the earliest phases of the host immune response through Salmonella-induced pathways, provide new approaches to develop strategies for SE prevention and treatment, and may enhance innate resistance by genetic selection in animals.

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“…Resident peritoneal macrophages were isolated using ice-cold PBS as previously described [ 11 , 57 ].…”

Section: Methodsmentioning

confidence: 99%

Macrophage-derived LTB4 promotes abscess formation and clearance of Staphylococcus aureus skin infection in mice

et al. 2018

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The early events that shape the innate immune response to restrain pathogens during skin infections remain elusive. Methicillin-resistant Staphylococcus aureus (MRSA) infection engages phagocyte chemotaxis, abscess formation, and microbial clearance. Upon infection, neutrophils and monocytes find a gradient of chemoattractants that influence both phagocyte direction and microbial clearance. The bioactive lipid leukotriene B4 (LTB4) is quickly (seconds to minutes) produced by 5-lipoxygenase (5-LO) and signals through the G protein-coupled receptors LTB4R1 (BLT1) or BLT2 in phagocytes and structural cells. Although it is known that LTB4 enhances antimicrobial effector functions in vitro, whether prompt LTB4 production is required for bacterial clearance and development of an inflammatory milieu necessary for abscess formation to restrain pathogen dissemination is unknown. We found that LTB4 is produced in areas near the abscess and BLT1 deficient mice are unable to form an abscess, elicit neutrophil chemotaxis, generation of neutrophil and monocyte chemokines, as well as reactive oxygen species-dependent bacterial clearance. We also found that an ointment containing LTB4 synergizes with antibiotics to eliminate MRSA potently. Here, we uncovered a heretofore unknown role of macrophage-derived LTB4 in orchestrating the chemoattractant gradient required for abscess formation, while amplifying antimicrobial effector functions.

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SOCS1 is a negative regulator of metabolic reprogramming during sepsis

Cited by 35 publications

References 91 publications

Glycine Relieves Intestinal Injury by Maintaining mTOR Signaling and Suppressing AMPK, TLR4, and NOD Signaling in Weaned Piglets after Lipopolysaccharide Challenge

Glycine Relieves Intestinal Injury by Maintaining mTOR Signaling and Suppressing AMPK, TLR4, and NOD Signaling in Weaned Piglets after Lipopolysaccharide Challenge

Messenger RNA Sequencing and Pathway Analysis Provide Novel Insights Into the Susceptibility to Salmonella enteritidis Infection in Chickens

Macrophage-derived LTB4 promotes abscess formation and clearance of Staphylococcus aureus skin infection in mice

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