MMP-9 Mediates Cross-Talk between Neutrophils and Endothelial Cells in Psoriasis

Alves‐Filho, José C.; Melo, Bruno Marcel Silva de; Ryffel, Bernhard

doi:10.1016/j.jid.2020.09.006

Cited by 12 publications

(8 citation statements)

References 5 publications

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“…Further analysis revealed that the attenuated severity of ALI in SIRP-alpha KO mice was associated with lower infiltrating Siglec-F(-) subtype of neutrophils and macrophages. Because neutrophils and macrophages are major sources of debilitating matrix metallopeptidase 2/9 (MMP2/9), ROS and other pro-inflammatory mediators ( 30 , 31 ), the reduced infiltration of neutrophils and macrophages should contribute to the beneficial effects of SIRP-alpha deficiency in murine ALI.…”

Section: Discussionmentioning

confidence: 99%

Soluble SIRP-Alpha Promotes Murine Acute Lung Injury Through Suppressing Macrophage Phagocytosis

et al. 2022

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Soluble signal regulatory protein-alpha (SIRP-alpha) is elevated in bronchoalveolar lavage (BAL) of mice with lipopolysaccharides (LPS)-induced acute lung injury (ALI). To define the role of soluble SIRP-alpha in the pathogenesis of ALI, we established murine ALI in wild-type (WT) and SIRP-alpha knock-out (KO) mice by intratracheal administration of LPS. The results indicated that lack of SIRP-alpha significantly reduced the pathogenesis of ALI, in association with attenuated lung inflammation, infiltration of neutrophils and expression of pro-inflammatory cytokines in mice. In addition, lack of SIRP-alpha reduced the expression of pro-inflammatory cytokines in LPS-treated bone marrow-derived macrophages (BMDMs) from KO mice, accompanied with improved macrophage phagocytosis. Blockade of soluble SIRP-alpha activity in ALI BAL by anti-SIRP-alpha antibody (aSIRP) effectively reduced the expression of TNF-alpha and IL-6 mRNA transcripts and proteins, improved macrophage phagocytosis in vitro. In addition, lack of SIRP-alpha reduced activation of Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1) and improved activation of signal transducer and activator of transcription-3 (STAT3) and STAT6. Suppression of SHP-1 activity by tyrosine phosphatase inhibitor 1 (TPI-1) increased activation of STAT3 and STAT6, and improved macrophage phagocytosis, that was effectively reversed by STAT3 and STAT6 inhibitors. Thereby, SIRP-alpha suppressed macrophage phagocytosis through activation of SHP-1, subsequently inhibiting downstream STAT3 and STAT6 signaling. Lack of SIRP-alpha attenuated murine ALI possibly through increasing phagocytosis, and improving STAT3 and STAT6 signaling in macrophages. SIRP-alpha would be promising biomarker and molecular target in the treatment of murine ALI and patients with acute respiratory distress syndrome (ARDS).

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Section: Discussionmentioning

confidence: 99%

Soluble SIRP-Alpha Promotes Murine Acute Lung Injury Through Suppressing Macrophage Phagocytosis

et al. 2022

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“…107,108 Specifically, elevated levels of MMP-9 and pro-MMP-1 levels were observed in patients’ serum, and MMP-3 was further correlated with cytokines IL-4, IL-17A, TNF-α in psoriatic patients. 107,109,110…”

Section: Resultsmentioning

confidence: 99%

The Mind Body Connection in Dermatologic Conditions: A Literature Review

Mar,

Rivers

2023

J Cutan Med Surg

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Psychodermatology pertains to the relationship between the skin and brain. This review aims to summarize the evidence of the mind body connection in four psychophysiological conditions: rosacea, atopic dermatitis (AD), acne vulgaris (AV), and psoriasis. A literature search was conducted using several English language databases. All four conditions share similar psychiatric co-morbidities, including but not limited to anxiety, depression, and suicidality. In rosacea, the upregulation of transient receptor potential vanilloid type 1, Toll like receptor 2, and Th17 cells releases downstream products that are simultaneously implicated in mood disorders. Stress exacerbates AV through the hypothalamic-pituitary-adrenal (HPA) system, which alters functioning of sebocytes and Cutibacterium acnes. In AD and psoriasis, the HPA axis influences Th1, Th2, Th22, and Th1, Th17 immune mediated responses, respectively. This leads to the secretion of pro-inflammatory cytokines which are also involved in the pathogenesis of anxiety and depression. Neurotransmitters implicated in mental illness, such as gamma-aminobutyric acid and serotonin, may also play a role in the development of AD and psoriasis. The management of cutaneous disease may mitigate psychological distress, and future research may show the corollary to also be true.

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“…[33] The results from the study of the pathogenesis of psoriasis reveal that the pharmacological inhibition of MMP-9 can reduce skin vasodilation, vascular permeability, and inflammation. [34] To date, more than 200 compounds have been isolated and identified from RA, including flavonoids, saponins, and polysaccharides. [35,36] Among them, RA polysaccharides, flavonoids, and Astragaloside IV are 3 classes of beneficial compounds closely related to the pharmacological activity and therapeutic effect of RA.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Predicting the anti-inflammatory mechanism of Radix Astragali using network pharmacology and molecular docking

Ren,

Ding,

et al. 2023

Medicine

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According to current research, the primary active ingredients of Radix Astragali (RA), such as saponins, flavonoids, and polysaccharides, play an important role in anti-inflammatory effects. However, the exact molecular mechanism underlying the action was not elucidated to date. Our research attempted to determine the active components in RA and to investigate the interaction between the active components and targets involved in the anti-inflammation activity by network pharmacology and molecular docking. The active components and targets of RA were screened out by TCMSP. Thereafter, through the “anti-inflammation effect” and “inflammation” as the keywords, disease targets were obtained from the GeneCards database. The PPI network was constructed with Cytoscape 3.8.0 software to screen core targets. The GO function and KEGG analysis were enriched and analyzed through the Metascape platform, obtaining the 3-dimensional view of the core targets from the PDB database, and then, performing molecular docking in AutoDock Vina, a heatmap was constructed using the binding free energies in GraphPad Prism 8. The Discovery Studio software was used for docking analysis, and eventually, the docking results were visualized. We also explored the targets and signaling pathways of Astragaloside IV acting on anti-inflammatory effects via constructing compound-disease-target-pathway network. 18 active components and 45 targets of RA were screened out. The main anti-inflammatory active components of RA were quercetin, Astragaloside IV, kaempferol, 7-O-methylisomucronulatol, and formononetin, and the strongly interacting core proteins were TNF, IL6, IL1B, TLR4, CXCL8, CCL2, IL10, VEGFA, and MMP9. The signal pathways mainly involved include Lipid and atherosclerosis, IL-17 signaling pathway, Chagas disease, leishmaniasis, and TNF signaling pathway. Moreover, molecular docking showed that the 2 most active compounds, Astragaloside IV and kaempferol, could efficiently bind with the targets TNF, TLR4, and IL10. Astragaloside IV may play a part in anti-inflammatory effects through pathways such as HIF-1 signaling pathway, Inflammatory bowel disease and Hepatitis B ect. RA exhibits the characteristic of multicomponent and multitarget synergistic effects in exerting anti-inflammatory effects and the effective component of RA is Astragaloside IV, targeting TNF, TLR4, and IL10.

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MMP-9 Mediates Cross-Talk between Neutrophils and Endothelial Cells in Psoriasis

Cited by 12 publications

References 5 publications

Soluble SIRP-Alpha Promotes Murine Acute Lung Injury Through Suppressing Macrophage Phagocytosis

Soluble SIRP-Alpha Promotes Murine Acute Lung Injury Through Suppressing Macrophage Phagocytosis

The Mind Body Connection in Dermatologic Conditions: A Literature Review

Predicting the anti-inflammatory mechanism of Radix Astragali using network pharmacology and molecular docking

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