The role of Syk kinase in UV mediated skin damage

2021 ◽  
Author(s):  
Zhenyu Huang
Keyword(s):  
Skin Damage ◽  
Syk Kinase

scholarly journals The role of Syk kinase in ultraviolet-mediated skin damage

2011 ◽  
Vol 165 (1) ◽  
pp. 69-77 ◽  
Author(s):  
E. Papazoglou ◽  
Z.Y. Huang ◽  
C. Sunkari ◽  
J. Uitto
Keyword(s):  
Skin Damage ◽  
Syk Kinase

scholarly journals GSDMD contributes to host defence against Staphylococcus aureus skin infection by suppressing the Cxcl1–Cxcr2 axis

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Zhen-Zhen Liu ◽  
Yong-Jun Yang ◽  
Feng-Hua Zhou ◽  
Ke Ma ◽  
Xiao-Qi Lin ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Skin Infection ◽  
Bacterial Colonization ◽  
Critical Role ◽  
Host Defence ◽  
Skin Damage ◽  
Microbial Infection ◽  
Caspase 1 ◽  
Deficient Mice

AbstractGasdermin D (GSDMD), a member of the gasdermin protein family, is a caspase substrate, and its cleavage is required for pyroptosis and IL-1β secretion. To date, the role and regulatory mechanism of GSDMD during cutaneous microbial infection remain unclear. Here, we showed that GSDMD protected against Staphylococcus aureus skin infection by suppressing Cxcl1–Cxcr2 signalling. GSDMD deficiency resulted in larger abscesses, more bacterial colonization, exacerbated skin damage, and increased inflammatory cell infiltration. Although GSDMD deficiency resulted in defective IL-1β production, the critical role of IL-1β was counteracted by the fact that Caspase-1/11 deficiency also resulted in less IL-1β production but did not aggravate disease severity during S. aureus skin infection. Interestingly, GSDMD-deficient mice had increased Cxcl1 secretion accompanied by increased recruitment of neutrophils, whereas Caspase-1/11-deficient mice presented similar levels of Cxcl1 and neutrophils as wild-type mice. Moreover, the absence of GSDMD promoted Cxcl1 secretion in bone marrow-derived macrophages induced by live, dead, or different strains of S. aureus. Corresponding to higher transcription and secretion of Cxcl1, enhanced NF-κB activation was shown in vitro and in vivo in the absence of GSDMD. Importantly, inhibiting the Cxcl1–Cxcr2 axis with a Cxcr2 inhibitor or anti-Cxcl1 blocking antibody rescued host defence defects in the GSDMD-deficient mice. Hence, these results revealed an important role of GSDMD in suppressing the Cxcl1–Cxcr2 axis to facilitate pathogen control and prevent tissue damage during cutaneous S. aureus infection.

scholarly journals Kynurenine Pathway in Skin Cells: Implications for UV-Induced Skin Damage

2012 ◽  
Vol 5 ◽  
pp. IJTR.S9835 ◽  
Author(s):  
Diba Sheipouri ◽  
Nady Braidy ◽  
Gilles J. Guillemin
Keyword(s):  
Amino Acid ◽  
Essential Amino Acid ◽  
Ultra Violet ◽  
Kynurenine Pathway ◽  
Uv Exposure ◽  
Skin Damage ◽  
Skin Cells ◽  
Amino Acid Tryptophan ◽  
Inflammatory Component

The kynurenine pathway (KP) is the principle route of catabolism of the essential amino acid tryptophan, leading to the production of several neuroactive and immunoregulatory metabolites. Alterations in the KP have been implicated in various neuropsychiatric and neurodegenerative diseases, immunological disorders, and many other diseased states. Although the role of the KP in the skin has been evaluated in small niche fields, limited studies are available regarding the effect of acute ultra violet exposure and the induction of the KP in human skin-derived fibroblasts and keratinocytes. Since UV exposure can illicit an inflammatory component in skin cells, it is highly likely that the KP may be induced in these cells in response to UV exposure. It is also possible that some KP metabolites may act as pro-inflammatory and anti-inflammatory mediators, since the KP is important in immunomodulation.

scholarly journals Critical role of Src-Syk-PLCγ2 signaling in megakaryocyte migration and thrombopoiesis

Blood ◽  
2010 ◽  
Vol 116 (5) ◽  
pp. 793-800 ◽  
Author(s):  
Alexandra Mazharian ◽  
Steve G. Thomas ◽  
Tarvinder S. Dhanjal ◽  
Christopher D. Buckley ◽  
Steve P. Watson
Keyword(s):  
Kinase Inhibitor ◽  
Tyrosine Phosphatase ◽  
Critical Role ◽  
Src Family Kinases ◽  
Surface Glycoprotein ◽  
Platelet Recovery ◽  
Glycoprotein Vi ◽  
Syk Kinase ◽  
And Migration

Migration of megakaryocytes (MKs) from the proliferative osteoblastic niche to the capillary-rich vascular niche is essential for proplatelet formation and platelet release. In this study, we explore the role of surface glycoprotein receptors and signaling proteins in regulating MK migration and platelet recovery after immune-induced thrombocytopenia. We show that spreading and migration of mouse primary bone marrow–derived MKs on a fibronectin matrix are abolished by the Src family kinases inhibitor PP1, the Syk kinase inhibitor R406 and the integrin αIIbβ3 antagonist lotrafiban. We also demonstrate that these responses are inhibited in primary phospholipase C γ2 (PLCγ2)–deficient MKs. Conversely, MK spreading and migration were unaltered in the absence of the collagen receptor, the glycoprotein VI–FcRγ-chain complex. We previously reported a correlation between a defect in MK migration and platelet recovery in the absence of platelet endothelial cell adhesion molecule-1 and the tyrosine phosphatase CD148. This correlation also holds for mice deficient in PLCγ2. This study identifies a model in which integrin signaling via Src family kinases and Syk kinase to PLCγ2 is required for MK spreading, migration, and platelet formation.

scholarly journals The role of bacterial cellulose loaded with plant phenolics in prevention of UV-induced skin damage

2021 ◽  
pp. 100122
Author(s):  
Isabela de Andrade Arruda Fernandes ◽  
Giselle Maria Maciel ◽  
Valéria Rampazzo Ribeiro ◽  
Raquel Rossetto ◽  
Alessandra Cristina Pedro ◽  
...  
Keyword(s):  
Bacterial Cellulose ◽  
Plant Phenolics ◽  
Skin Damage

scholarly journals Key role of integrin αIIbβ3 signaling to Syk kinase in tissue factor-induced thrombin generation

2012 ◽  
Vol 69 (20) ◽  
pp. 3481-3492 ◽  
Author(s):  
Paola E. J. van der Meijden ◽  
Marion A. H. Feijge ◽  
Frauke Swieringa ◽  
Karen Gilio ◽  
Reyhan Nergiz-Unal ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Thrombin Generation ◽  
Integrin Αiibβ3 ◽  
Syk Kinase

scholarly journals Exopolysaccharide from Lactobacillus plantarum HY7714 Protects against Skin Aging through Skin–Gut Axis Communication

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1651
Author(s):  
Kippeum Lee ◽  
Hyeon Ji Kim ◽  
Soo A Kim ◽  
Soo-Dong Park ◽  
Jae-Jung Shim ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Lactobacillus Plantarum ◽  
Skin Diseases ◽  
Therapeutic Potential ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Skin Damage ◽  
Genes Encoding ◽  
Natural Result

Skin aging occurs inevitably as a natural result of physiological changes over time. In particular, solar exposure of the skin accounts for up to 90% of skin damage. Numerous studies have examined the ability of dietary constituents to prevent skin aging, and recent research has emphasized the role of functional probiotics in intestinal function and skin aging. However, the mechanism of the interactions between aging and probiotics has not been elucidated yet. The aim of this study was to determine the role of exopolysaccharides (EPS) produced by lactic acid bacteria (LAB) identified as Lactobacillus plantarum HY7714 in regulating tight junctions in intestinal epithelial cells and increasing moisture retention in human dermal fibroblasts cells. We observed that HY7714 EPS controlled intestinal tight junctions in Caco-2 cells by upregulating the genes encoding occludin-1 (OCL-1) and zonula occluden-1 (ZO-1). In addition, HY7714 EPS effectively improved UVB-induced cytotoxicity and hydration capacity in HS68 cells by downregulating production of metalloproteinases (MMPs) and reactive oxygen species (ROS). In summary, HY7714 EPS is an effective anti-aging molecule in skin and may have therapeutic potential against skin diseases and UVB-induced damage. Therefore, HY7714 EPS serves as a functional substance in skin–gut axis communication.

scholarly journals Chemical genetics strategy to profile kinase target engagement reveals role of FES in neutrophil phagocytosis via SYK activation

2019 ◽  
Author(s):  
Tom van der Wel ◽  
Riet Hilhorst ◽  
Hans den Dulk ◽  
Tim van den Hooven ◽  
Nienke M. Prins ◽  
...  
Keyword(s):  
Fluorescent Probe ◽  
Chemical Genetics ◽  
Binding Pocket ◽  
Myeloid Differentiation ◽  
Target Engagement ◽  
Syk Kinase ◽  
Promising Therapeutic Target ◽  
Single Oxygen Atom ◽  
Single Oxygen

AbstractChemical tools and methods that report on target engagement of endogenously expressed protein kinases by small molecules in human cells are highly desirable. Here, we describe a chemical genetics strategy that allows the study of non-receptor tyrosine kinase FES, a promising therapeutic target for cancer and immune disorders. Precise gene editing was used in combination with a rationally designed, complementary fluorescent probe to visualize endogenous FES kinase in HL-60 cells. We replaced a single oxygen atom by a sulphur in a serine residue at the DFG-1 position of the ATP-binding pocket in an endogenously expressed kinase, thereby sensitizing the engineered protein towards covalent labeling and inactivation by a fluorescent probe. The temporal control offered by this strategy allows acute inactivation of FES activity both during myeloid differentiation and in terminally differentiated neutrophils. Our results show that FES activity is dispensable for differentiation of HL-60 cells towards macrophages. Instead, FES plays a key role in neutrophil phagocytosis by activation of SYK kinase, a central regulator of immune function in neutrophils. This strategy holds promise as a target validation method for kinases.

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