Dataset Information

Concentrated growth factor regulates the macrophage-mediated immune response

ABSTRACT: Abstract Concentrated growth factor (CGF) is a promising regenerative material that serves as a scaffold and adjunct growth factor for tissue engineering. The host immune response, particularly macrophage activity, plays a critical role in injury repair and tissue regeneration. However, the biological effect of CGF on the immune response is not clear. To enrich the theoretical groundwork for clinical application, the present study examined the immunoregulatory role of CGF in macrophage functional activities in vitro. The CGF scaffold appeared as a dense fibrin network with multiple embedded leukocytes and platelets, and it was biocompatible with macrophages. Concentrated bioactive factors in the CGF extract enhanced THP-1 monocyte recruitment and promoted the maturation of suspended monocytes into adherent macrophages. CGF extract also promoted THP-1 macrophage polarization toward the M2 phenotype with upregulated CD163 expression, as detected by cell morphology and surface marker expression. A cytokine antibody array showed that CGF extract exerted a regulatory effect on macrophage functional activities by reducing secretion of the inflammatory factor interleukin-1β while inducing expression of the chemokine regulated on activation, normal T cell expressed and secreted. Mechanistically, the AKT signaling pathway was activated, and an AKT inhibitor partially suppressed the immunomodulatory effect of CGF. Our findings reveal that CGF induces a favorable immune response mediated by macrophages, which represents a promising strategy for functional tissue regeneration.

SUBMITTER: Luo H

PROVIDER: S-EPMC8421811 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveHigh-expression alleles of macrophage migration inhibitory factor (MIF) are linked genetically to the severity of systemic lupus erythematosus (SLE). The U1 small nuclear RNP (snRNP) immune complex containing U1 snRNP and anti-U1 snRNP antibodies, which are found in patients with SLE, activates the NLRP3 inflammasome, comprising NLRP3, ASC, and procaspase 1, in human monocytes, leading to the production of interleukin-1β (IL-1β). This study was undertaken to investigate the role of the snRNP immune complex in up-regulating the expression of MIF and its interface with the NLRP3 inflammasome.MethodsMIF, IL-1β, NLRP3, caspase 1, ASC, and MIF receptors were analyzed by enzyme-linked immunosorbent assay, Western blotting, quantitative polymerase chain reaction, and cytometry by time-of-flight mass spectrometry (CytoF) in human monocytes incubated with or without the snRNP immune complex. MIF pathway responses were probed with the novel small molecule antagonist MIF098.ResultsThe snRNP immune complex induced the production of MIF and IL-1β from human monocytes. High-dimensional, single-cell CytoF analysis established that MIF regulates activation of the NLRP3 inflammasome, including findings of a quantitative relationship between MIF and its receptors and IL-1β levels in the monocytes. MIF098, which blocks MIF binding to its cognate receptor, suppressed the production of IL-1β, the up-regulation of NLRP3, which is a rate-limiting step in NLRP3 inflammasome activation, and the activation of caspase 1 in snRNP immune complex-stimulated human monocytes.ConclusionThe U1 snRNP immune complex is a specific stimulus of MIF production in human monocytes, with MIF having an upstream role in defining the inflammatory characteristics of activated monocytes by regulating NLRP3 inflammasome activation and downstream IL-1β production. These findings provide mechanistic insight and a therapeutic rationale for targeting MIF in subgroups of lupus patients, such as those classified as high genotypic MIF expressers or those with anti-snRNP antibodies.

Project description:BackgroundPlants are continuously challenged with biotic stress from environmental pathogens, and precise regulation of defense responses is critical for plant survival. Defense systems require considerable amounts of energy and resources, impairing plant growth, and plant hormones controlling transcriptional regulation play essential roles in establishing the appropriate balance between defense response to pathogens and growth. Chromatin regulators modulating gene transcription are broadly involved in regulating stress-responsive genes. However, which chromatin factors are involved in coordinating hormone signaling and immune responses in plants, and their functional mechanisms, remains unclear. Here, we identified a role of bromodomain-containing protein GTE4 in negatively regulating defense responses in Arabidopsis thaliana.ResultsGTE4 mainly functions as activator of gene expression upon infection with Pseudomonas syringe. Genome-wide profiling of GTE4 occupancy shows that GTE4 tends to bind to active genes, including ribosome biogenesis related genes and maintains their high expression levels during pathogen infection. However, GTE4 is also able to repress gene expression. GTE4 binds to and represses jasmonate biosynthesis gene OPR3. Disruption of GTE4 results in overaccumulation of jasmonic acid (JA) and enhanced JA-responsive gene expression. Unexpectedly, over-accumulated JA content in gte4 mutant is coupled with downregulation of JA-mediated immune defense genes and upregulation of salicylic acid (SA)-mediated immune defense genes, and enhanced resistance to Pseudomonas, likely through a noncanonical pathway.ConclusionsOverall, we identified a new role of the chromatin factor GTE4 as negative regulator of plant immune response through inhibition of JA biosynthesis, which in turn noncanonically activates the defense system against Pseudomonas. These findings provide new knowledge of chromatic regulation of plant hormone signaling during defense responses.

Dataset Information

Concentrated growth factor regulates the macrophage-mediated immune response

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets