Systemic inflammatory response syndrome (SIRS) is a highly mortal inflammatory disease, associated with systemic inflammation and organ dysfunction. SIRS can have a sterile cause or can be initiated by an infection, called sepsis. The prevalence is high, and available treatments are ineffective and mainly supportive. Consequently, there is an urgent need for new treatments. The brain is one of the first organs affected during SIRS, and sepsis and the consequent neurological complications, such as encephalopathy, are correlated with decreased survival. The choroid plexus (CP) that forms the blood-CSF barrier (BCSFB) is thought to act as a brain "immune sensor" involved in the communication between the peripheral immune system and the CNS. Nevertheless, the involvement of BCSFB integrity in systemic inflammatory diseases is seldom investigated. We report that matrix metalloprotease-8 (MMP8) depletion or inhibition protects mice from death and hypothermia in sepsis and renal ischemia/reperfusion. This effect could be attributed to MMP8-dependent leakage of the BCSFB, caused by collagen cleavage in the extracellular matrix of CP cells, which leads to a dramatic change in cellular morphology. Disruption of the BCSFB results in increased CSF cytokine levels, brain inflammation, and downregulation of the brain glucocorticoid receptor. This receptor is necessary for dampening the inflammatory response. Consequently, MMP8(+/+) mice, in contrast to MMP8(-/-) mice, show no anti-inflammatory response and this results in high mortality. In conclusion, we identify MMP8 as an essential mediator in SIRS and, hence, a potential drug target. We also propose that the mechanism of action of MMP8 involves disruption of the BCSFB integrity.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6621276 | PMC |
http://dx.doi.org/10.1523/JNEUROSCI.0967-12.2012 | DOI Listing |
Lipids Health Dis
January 2025
Department of Pediatrics, West China Second University Hospital, Sichuan University, No. 20, Section 3, South Renmin Road, Chengdu, Sichuan Province, 610041, China.
Background: This study aimed to investigate the association between relative fat mass (RFM) and asthma, as well as to explore the mediating role of Systemic Immune-Inflammation Index (SII) and Systemic Inflammation Response Index (SIRI).
Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey from 2007 to 2018. Associations between RFM and asthma were tested using multivariable logistic regressions, restricted cubic splines, subgroup analyses, and interaction tests, with mediation analysis for SII and SIRI.
BMC Pulm Med
January 2025
Department of Respiratory Medicine, The First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), 1882 South Zhonghuan Road, Jiaxing, Zhejiang, 314000, China.
Background: Lung health is intricately linked with inflammation. The pan-immune-inflammation value (PIV) emerges as a promising biomarker, offering reflection into systemic inflammatory states and assisting in the prognosis of diverse diseases. This research aims to explore the associations between PIV and respiratory symptoms, respiratory diseases and lung function.
View Article and Find Full Text PDFSci Rep
January 2025
Nantong University Hospital, Nantong, Jiangsu, People's Republic of China.
Sepsis is a severe infectious disease with high mortality. However, the indicators used to evaluate its severity and prognosis are relatively complicated. The systemic inflammatory response index (SIRI), a new inflammatory indicator, has shown good predictive value in chronic infection, stroke, and cancer.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Dermatology, University of Maryland School of Medicine, 419 West Redwood Street, Suite 235, Baltimore, MD, 21201, USA.
Erythroderma is a severe and heterogeneous inflammatory skin condition with little guidance on the approach to management in cases of unknown etiology. To guide therapeutic selection, we sought to create an immunophenotyping platform able to identify aberrant cell populations and cytokines in subtypes of erythroderma. We performed high-parameter flow cytometry on peripheral blood mononuclear cells (PBMCs) and whole blood of a patient with refractory idiopathic erythroderma, erythrodermic patients with Sézary syndrome and pityriasis rubra pilaris, and healthy controls.
View Article and Find Full Text PDFNat Commun
January 2025
National Institute of Health and Medical Research (INSERM) UMRS-976 HIPI, Paris Cité University, Saint-Louis Hospital, 75010, Paris, France.
Endotypes are characterized by the immunological, inflammatory, metabolic, and remodelling pathways that explain the mechanisms underlying the clinical presentation (phenotype) of a disease. Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease caused by COL7A1 pathogenic variants. Although underscored by animal studies, the endotypes of human RDEB are poorly understood.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!