scholarly journals Effects of (–)-Loliolide against Fine Dust Preconditioned Keratinocyte Media-Induced Dermal Fibroblast Inflammation

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 675
Author(s):  
Ilekuttige Priyan Shanura Fernando ◽  
Mawalle Kankanamge Hasitha Madhawa Dias ◽  
Dissanayaka Mudiyanselage Dinesh Madusanka ◽  
Hyun-Soo Kim ◽  
Eui-Jeong Han ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Dermal Fibroblast ◽  
Pulmonary Complications ◽  
Mitogen Activated Protein Kinase ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Fine Dust ◽  
Elastase Activity ◽  
Therapeutic Role ◽  
Extracellular Matrix Components

At present air pollution in parts of East Asia is at an alarming level due to elevated levels of fine dust (FD). Other than pulmonary complications, FD was found to affect the pathogenesis of ROS-dependent inflammatory responses via penetrating barrier-disrupted skin, leading to degradation of extracellular matrix components through the keratinocyte-fibroblast axis. The present study discloses the evaluation of human dermal fibroblast (HDF) responses to FD preconditioned human keratinocyte media (HPM) primed without and with (-)-loliolide (HTT). HPM-FD treatment increased the ROS level in HDFs and activated mitogen-activated protein kinase-derived nuclear factor (NF)-κB inflammatory signaling pathways with a minor reduction of viability. The above events led to cell differentiation and production of matrix metalloproteinases (MMP), increasing collagenase and elastase activity despite the increase of tissue inhibitors of metalloproteinases (TIMP). Media from HTT primed keratinocytes stimulated with FD indicated ameliorated levels of MMPs, inflammatory cytokines, and chemokines in HDFs with suppressed collagenase and elastase activity. Present observations help to understand the factors that affect HDFs in the microenvironment of FD exposed keratinocytes and the therapeutic role of HTT as a suppressor of skin aging. Further studies using organotypic skin culture models could broaden the understanding of the effects of FD and the therapeutic role of HTT.

scholarly journals An unconventional role of an ASB family protein in NF-κB activation and inflammatory response during microbial infection and colitis

2021 ◽  
Vol 118 (3) ◽  
pp. e2015416118
Author(s):  
Panpan Hou ◽  
Penghui Jia ◽  
Kongxiang Yang ◽  
Zibo Li ◽  
Tian Tian ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathways ◽  
Crucial Role ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Mitogen Activated Protein Kinase ◽  
Cytokine Signaling ◽  
Microbial Infection ◽  
The Stability

Nuclear factor κB (NF-κB)–mediated signaling pathway plays a crucial role in the regulation of inflammatory process, innate and adaptive immune responses. The hyperactivation of inflammatory response causes host cell death, tissue damage, and autoinflammatory disorders, such as sepsis and inflammatory bowel disease. However, how these processes are precisely controlled is still poorly understood. In this study, we demonstrated that ankyrin repeat and suppressor of cytokine signaling box containing 1 (ASB1) is involved in the positive regulation of inflammatory responses by enhancing the stability of TAB2 and its downstream signaling pathways, including NF-κB and mitogen-activated protein kinase pathways. Mechanistically, unlike other members of the ASB family that induce ubiquitination-mediated degradation of their target proteins, ASB1 associates with TAB2 to inhibit K48-linked polyubiquitination and thereby promote the stability of TAB2 upon stimulation of cytokines and lipopolysaccharide (LPS), which indicates that ASB1 plays a noncanonical role to further stabilize the target protein rather than induce its degradation. The deficiency of Asb1 protects mice from Salmonella typhimurium– or LPS-induced septic shock and increases the survival of mice. Moreover, Asb1-deficient mice exhibited less severe colitis and intestinal inflammation induced by dextran sodium sulfate. Given the crucial role of ASB proteins in inflammatory signaling pathways, our study offers insights into the immune regulation in pathogen infection and inflammatory disorders with therapeutic implications.

P38α Deficiency in Macrophages Ameliorates Murine Experimental Colitis by Regulating Inflammation and Immune Process

2021 ◽  
Author(s):  
Wei Chen ◽  
Rui Liang ◽  
Youcai Yi ◽  
Xiaoyu Chen ◽  
Huining Fan ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Experimental Colitis ◽  
Mitogen Activated Protein Kinase ◽  
Fish Analysis ◽  
Related Factors ◽  
Normal Tissues ◽  
P38 Mapk Inhibitors

Abstract Introduction: P38α is a mitogen-activated protein kinase (MAPK) that mediates inflammatory responses. P38α alterations have been associated with the inflammation-related diseases. However, the role of macrophages-derived p38α in dextran sulfate sodium (DSS)-induced murine experimental colitis remains unclear.Objectives: We characterized the role of macrophages-derived p38α in DSS-induced colitis.Methods: The expression of macrophage-derived p38α in human colitis and normal tissues was measured by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis. Macrophage-specific p38α knockout (p38αΔMφ) and wild type (WT) mice administrated by 3% DSS were used to establish experimental colitis. The alterations in inflammatory cytokines, intestinal epithelial barrier, cell proliferation and cell apoptosis between p38αΔMφ and WT groups were determined by IHC, immunofluorescence (IF), TdT-mediated dUTP Nick-End Labeling (TUNEL) and Western blot analyses. The enriched pathways between p38αΔMφ and WT groups were identified by RNA-seq and KEGG analysis. SB203580 and BIRB796 as the p38 MAPK inhibitors were used to treat DSS-induced colitis. Results: p38α was co-localized with CD68 in the cytoplasm and their co-expression indicated an increased level in colitis tissues as compared with the normal tissues. P38α deficiency in macrophages was sufficient to suppress the exacerbated clinical symptoms and inflammation responses in experimental colitis, followed by reducing cytokine release, increasing MUC-2 and Claudin-2 secretion and promoting colonic mucosa repair. Further investigations validated that the immune process-related factors such as Lgals9, Rtp4, Ddx60, Nlrp1b, Hsh2d, Oas2 and Oas3 were upregulated in colon tissues from p38αΔMφ group as compared with the WT group. Inhibition of p38 MAPK attenuated DSS-induced colitis. Conclusion: Our findings demonstrated that p38α deficiency in macrophages ameliorated murine experimental colitis by regulating inflammation and immune process.

scholarly journals P38α Deficiency in Macrophages Ameliorates Murine Experimental Colitis by Regulating Inflammation and Immune Process

2021 ◽  
Author(s):  
Wei Chen ◽  
Rui Liang ◽  
Youcai Yi ◽  
Xiaoyu Chen ◽  
Huining Fan ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Experimental Colitis ◽  
Mitogen Activated Protein Kinase ◽  
Fish Analysis ◽  
Related Factors ◽  
Normal Tissues ◽  
P38 Mapk Inhibitors

Abstract Introduction: P38α is a mitogen-activated protein kinase (MAPK) that mediates inflammatory responses. P38α alterations have been associated with the inflammation-related diseases. However, the role of macrophages-derived p38α in dextran sulfate sodium (DSS)-induced murine experimental colitis remains unclear.Objectives: We characterized the role of macrophages-derived p38α in DSS-induced colitis.Methods: The expression of macrophage-derived p38α in human colitis and normal tissues was measured by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis. Macrophage-specific p38α knockout (p38αΔMφ) and wild type (WT) mice administrated by 3% DSS were used to establish experimental colitis. The alterations in inflammatory cytokines, intestinal epithelial barrier, cell proliferation and cell apoptosis between p38αΔMφ and WT groups were determined by IHC, immunofluorescence (IF), TdT-mediated dUTP Nick-End Labeling (TUNEL) and Western blot analyses. The enriched pathways between p38αΔMφ and WT groups were identified by RNA-seq and KEGG analysis. SB203580 and BIRB796 as the p38 MAPK inhibitors were used to treat DSS-induced colitis. Results: p38α was co-localized with CD68 in the cytoplasm and their co-expression indicated an increased level in colitis tissues as compared with the normal tissues. P38α deficiency in macrophages was sufficient to suppress the exacerbated clinical symptoms and inflammation responses in experimental colitis, followed by reducing cytokine release, increasing MUC-2 and Claudin-2 secretion and promoting colonic mucosa repair. Further investigations validated that the immune process-related factors such as Lgals9, Rtp4, Ddx60, Nlrp1b, Hsh2d, Oas2 and Oas3 were upregulated in colon tissues from p38αΔMφ group as compared with the WT group. Inhibition of p38 MAPK attenuated DSS-induced colitis. Conclusion: Our findings demonstrated that p38α deficiency in macrophages ameliorated murine experimental colitis by regulating inflammation and immune process.

Designing TIMP (tissue inhibitor of metalloproteinases) variants that are selective metalloproteinase inhibitors

2003 ◽  
Vol 70 ◽  
pp. 201-212 ◽  
Author(s):  
Hideaki Nagase ◽  
Keith Brew
Keyword(s):  
Three Dimensional ◽  
Therapeutic Interventions ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Structural Basis ◽  
Structural Elements ◽  
Ridge Structure ◽  
Extracellular Matrix Components ◽  
Metalloproteinase Inhibitors ◽  
The Matrix ◽  
A Disintegrin And Metalloproteinase

The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs), enzymes that play central roles in the degradation of extracellular matrix components. The balance between MMPs and TIMPs is important in the maintenance of tissues, and its disruption affects tissue homoeostasis. Four related TIMPs (TIMP-1 to TIMP-4) can each form a complex with MMPs in a 1:1 stoichiometry with high affinity, but their inhibitory activities towards different MMPs are not particularly selective. The three-dimensional structures of TIMP-MMP complexes reveal that TIMPs have an extended ridge structure that slots into the active site of MMPs. Mutation of three separate residues in the ridge, at positions 2, 4 and 68 in the amino acid sequence of the N-terminal inhibitory domain of TIMP-1 (N-TIMP-1), separately and in combination has produced N-TIMP-1 variants with higher binding affinity and specificity for individual MMPs. TIMP-3 is unique in that it inhibits not only MMPs, but also several ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin motifs) metalloproteinases. Inhibition of the latter groups of metalloproteinases, as exemplified with ADAMTS-4 (aggrecanase 1), requires additional structural elements in TIMP-3 that have not yet been identified. Knowledge of the structural basis of the inhibitory action of TIMPs will facilitate the design of selective TIMP variants for investigating the biological roles of specific MMPs and for developing therapeutic interventions for MMP-associated diseases.

Therapeutic role of cell kinetics in acute leukaemia

1978 ◽  
Vol 7 (2) ◽  
pp. 339-362 ◽  
Author(s):  
Zalmen A. Arlin ◽  
Jerrold Fried ◽  
Bayard D. Clarkson
Keyword(s):  
Acute Leukaemia ◽  
Cell Kinetics ◽  
Therapeutic Role

In vitro studies reveal a potential therapeutic role of the combination of biguanides and statins for the treatment of prostate cancer

2018 ◽  
Author(s):  
Vicente Herrero-Aguayo ◽  
Juan M Jimenez-Vacas ◽  
Enrique Gomez-Gomez ◽  
Antonio J Leon-Gonzalez ◽  
Prudencio Saez-Martinez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
In Vitro Studies ◽  
Therapeutic Role ◽  
Potential Therapeutic Role
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