Similar Datasets
Project description:Il-1/MyD88-Dependent G-CSF and IL-6 Secretion Mediates Post Burn Anemia
| PRJNA886847 | ENA
Project description:The anemia of critical illness (ACI) is a nearly universal pathophysiological consequence of burn injury and a primary reason burn patients require massive quantities of transfused blood. Inflammatory processes are expected to drive postburn ACI and prevent meaningful erythropoietic stimulation through iron or erythropoietin supplementation, but to this day no specific inflammatory pathways have been identified as a critical mechanism. In this study, we examined whether secretion of G-CSF and IL-6 mediates distinct features of postburn ACI and interrogated inflammatory mechanisms that could be responsible for their secretion. Our analysis of mouse and human skin samples identified the burn wound as a primary source of G-CSF and IL-6 secretion. We show that G-CSF and IL-6 are secreted independently through an IL-1/MyD88-dependent mechanism, and we ruled out TLR2 and TLR4 as critical receptors. Our results indicate that IL-1/MyD88-dependent G-CSF secretion plays a key role in impairing medullary erythropoiesis and IL-6 secretion plays a key role in limiting the access of erythroid cells to iron. Importantly, we found that IL-1α/β neutralizing Abs broadly attenuated features of postburn ACI that could be attributed to G-CSF or IL-6 secretion and rescued deficits of circulating RBC counts, hemoglobin, and hematocrit caused by burn injury. We conclude that wound-based IL-1/MyD88 signaling mediates postburn ACI through induction of G-CSF and IL-6 secretion.
| S-EPMC10038902 | biostudies-literature
Project description:Macrophages are critical mediators of tissue homeostasis, cell proliferation, angiogenesis and tumor metastasis. The presence of TAMs is generally associated with tumor-promoting immunosuppressive function in solid tumors. These macrophages are widely acknowledged as one of the central suppressive populations within tumors, blocking effective T-cell responses. In the present study, we examined the transcriptional landscape of adaptor molecules downstream of TLRs in human cancers and found that higher expression of MYD88 is very well correlated with the tumor progression. In addition, we also found that mouse MyD88 but not TRIF, is essential for tumor progression and angiogenesis in melanoma. Interestingly, MyD88 is critical to maintain the immunosuppressive phenotype of TAMs in the tumors. Moreover, we found that interleukin-1 receptor (IL-1R)-Myd88 axis regulates programmed cell death (PD)-1 expression on TAMs by promoting the recruitment of phospho-NF-κB p65 to the CR-C region of the Pdcd1 promoter. Using myeloid-cell specific MyD88 mutant mice, we also showed that MyD88 expression in myeloid cells alone is sufficient to drive the melanoma progression. Thus, IL-1R/MyD88 axis maintains the immunosuppressive function of tumor-tissue macrophages to promote tumor growth by regulating PD-1/PD-L1 expression
2021-03-26 | GSE137046 | GEO
Project description:Transcriptome analysis of submandibular glands in female MyD88+/+ and MyD88−/− NOD mice. Sjögren's syndrome (SS) is an autoimmune disease characterized by dysfunction of salivary glands (SGs) and lacrimal glands, which is caused by chronic inflammation associated with autoantibody and autoreactive lymphocyte infiltration. The pathogenic mechanism of SS has not been fully elucidated. Infiltrated lymphocytes form regularized structures similar to lymphoid follicles of secondary lymphoid organs, such as T/B cell compartments, high endothelial venules (HEVs), lymphatic vessels, and germinal centers, therefore being believed as an ectopic lymphoid tissue called tertiary lymphoid organs (TLO). We previously found that deletion of the Toll-like receptor/IL-1 receptor (TLR/IL-1R) adaptor molecule gene Myd88 in SS model mice NOD reduced the frequency of lymphocyte infiltration and HEV formation in SGs. In this study, we analyzed the effect of MyD88 deficiency on lymphoid follicle formation in SGs of NOD mice. Microarray analysis showed decreased expression of genes related to TLO, such as Cxcl13 and Cxcr5, in Myd88-deficient SGs. These results indicate that deficiency of TLR/IL-1R signaling decrease gene expression ot chemokines in SGs, suggesting MyD88-dependent signaling is directly involved in formation of lymphoid follicles in SS.
2021-09-01 | GSE157669 | GEO
Project description:#G017 Burn/Trauma Study. This is a Glue Grant Study comparison between gene expression analyses performed in eight trauma/burn subjects using either a buffy coat isolation of whole blood or using the PAXgene system Keywords: other
2004-04-24 | GSE1343 | GEO
Project description:IL-36 cytokines have recently emerged as mediators of inflammation in autoimmune conditions including psoriasis vulgaris (PsV) and generalized pustular psoriasis (GPP). This study used RNA-seq to profile the transcriptome of primary epidermal keratinocytes (KCs) treated with IL-1B, IL-36A, IL-36B or IL-36G. We identified some early IL-1B-specific responses (8 hours post-treatment), but nearly all late IL-1B responses were replicated by IL-36 cytokines (24 hours post-treatment). Type I and II interferon genes exhibited time-dependent response patterns, with early induction (8 hours) followed by no response or repression (24 hours). Altogether, we identified 225 differentially expressed genes (DEGs) with shared responses to all 4 cytokines at both time points (8 + 24 hours). These involved up-regulation of ligands (IL1A, IL1B, IL36G) and activating proteases (CTSS), but also up-regulation of inhibitors such as IL1RN and IL36RN. Shared IL-1B/IL-36 DEGs overlapped significantly with genes altered in PsV and GPP skin lesions, as well as genes near GWAS loci linked to autoimmune and autoinflammatory diseases (e.g., PsV, psoriatic arthritis, IBD, primary biliary cholangitis). Inactivation of MyD88 adapter protein using CRISPR/Cas9 completely abolished expression responses of such DEGs to IL-1B and IL-36G stimulation. These results provide a global view of IL-1B and IL-36 expression responses in epidermal KCs with fine-scale characterization of time-dependent and cytokine-specific response patterns. Our findings support an important role for IL-1B and IL-36 in autoimmune or autoinflammatory conditions and show that MyD88 adaptor protein mediates shared IL-1B/IL-36 responses.
2018-03-04 | GSE109182 | GEO
Project description:Animal experiments were performed with male Sprague-Dawley rats (Charles River Laboratories, Boston, MA) weighing 150 ? 200 grams. All experimental protocols used in this study were approved by the Subcommittee on Research Animal Care, Massachusetts General Hospital. Rats were individually housed in a temperature-controlled (25oC) and light-controlled room (12h light-dark cycle) and allowed to adjust to their new surroundings for at least 5 days prior to the experiment. Water and rat chow were provided ad libitum to the animals. On the day of the treatment, the animals were randomly divided into two groups, burned and sham-burned. The burn injury consisted of a full-skin-thickness scald burn of the dorsum, calculated to be ~ 20% of the rat?s total body surface area (TBSA), induced by immersing the designated area in boiling water for 10 s (45). Rats were resuscitated with an intra-peritoneal injection of sterile saline solution (1.5 mL/Kg body weight/% TBSA) immediately after burn. The mortality rate of this treatment was negligible. At each time point (1, 2, 4, and 7d), three animals belonging to each group were sacrificed, the liver and serum collected, and stored at ?80oC after being inflicted with 20% TBSA burn injury. Sham-burn rats (n=3) considered as the control were treated identically except that they were immersed into a 37oC water bath and immediately sacrificed to collect the livers. Keywords = Burn Liver microarray genechip time course Keywords: time-course
2005-10-11 | GSE1860 | GEO
Project description:Pseudomonas aeruginosa strain:burn wound | isolate:burn wound Genome sequencing
| PRJNA753640 | ENA
Project description:Burn wound blister fluid is a valuable matrix for understanding the biological pathways associated with burn injury. In this study, 152 blister fluid samples collected from paediatric burn wounds at two different hospitals were analysed using mass spectrometry proteomic techniques. The protein abundance profile at different days post-burn indicated that there were more proteins associated with cellular damage/repair in the first 24 hours, whereas after this point there were more proteins associated with antimicrobial defence and inflammation. The inflammatory proteins persisted at a high level in the blister fluid for more than 7 days. This may indicate that removal of burn blisters prior to two days post-burn is optimal to prevent excessive or prolonged inflammation in the wound environment. Additionally, many proteins associated with the neutrophil extracellular trap (NET) pathway were increased post-burn, further implicating NETs in the post-burn inflammatory response. NET inhibitors may therefore be a potential treatment to reduce post-burn inflammation and coagulation pathology and enhance burn wound healing outcomes.
2024-03-04 | PXD050003 | Pride
Project description:Burn injury remains a major clinical challenge to both survival and to quality of life. Its progressive, aberrant inflammation underlies the lethal dysfunction of various organs and the pain it induces is excruciating and notoriously difficult to manage. While it is known that burn injury’s complex local and disseminating pathology is orchestrated from the burned tissue, few studies have sought to characterise the local signalling environment. An enhanced understanding of the local and acutely temporally-dynamic processes defining burn injury and its progression is required for the development of novel therapeutic interventions. Microdialysis was used as an interstitial sampling technique, conducted over three hours post-burn. Samples were analysed by metabolomics and a multiplex cytokine immunoassay. Next-Generation sequencing libraries of the burn and control microdialysis sites were prepared to measure transcriptional changes potentially underlying the interstitial profile characterising burn injury.
2018-08-31 | GSE102811 | GEO