A5040812011- Immune cells in cancer
- Metabolism, Diabetes, and Cancer
- Autophagy in Disease and Therapy
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Inflammation biomarkers and pathways
- Immune Response and Inflammation
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Advanced Glycation End Products research
- NF-κB Signaling Pathways
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Neonatal Respiratory Health Research
- Phagocytosis and Immune Regulation
- Protease and Inhibitor Mechanisms
- Pancreatic function and diabetes
- Pulmonary Hypertension Research and Treatments
- Cell Adhesion Molecules Research
- Asthma and respiratory diseases
- Macrophage Migration Inhibitory Factor
- Erythrocyte Function and Pathophysiology
- Sirtuins and Resveratrol in Medicine
- Telomeres, Telomerase, and Senescence
- S100 Proteins and Annexins
- IL-33, ST2, and ILC Pathways
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
University of Alabama at Birmingham
2015-2024
Pulmonary and Allergy Associates
2013-2021
University of Alabama
2020
St. Vincent's Birmingham
2005-2020
Université Côte d'Azur
2014
Although metabolic conditions associated with an increased AMP/ATP ratio are primary factors in the activation of 5′-adenosine monophosphate-activated protein kinase (AMPK), a number recent studies have shown that intracellular levels reactive oxygen species can stimulate AMPK activity, even without decrease cellular ATP. We found exposure recombinant AMPKαβγ complex or HEK 293 cells to H<sub>2</sub>O<sub>2</sub> was activity and also resulted oxidative modification AMPK, including...
Abstract High mobility group box 1 protein (HMGB1), originally characterized as a nuclear DNA-binding protein, has also been described to have an extracellular role when it is involved in cellular activation and proinflammatory responses. In this study, FLAG-tagged HMGB1 was inducibly expressed the presence of culture media with or without added IL-1β, IFN-γ, TNF-α. purified from cells grown alone only minimally increased cytokine production by MH-S macrophages had no effect on murine...
Although neutrophil extracellular traps (NETs) form to prevent dissemination of pathogenic microorganisms, excessive release DNA and DNA-associated proteins can also perpetuate sterile inflammation. In this study, we found that the danger-associated molecular pattern protein high-mobility group box 1 (HMGB1) induce NET formation. formation was after exposure wild-type receptor for advanced glycation end products-deficient HMGB1, whereas deficiency Toll-like (TLR)4 diminished ability...
AMP-activated protein kinase (AMPK) is activated by increases in the intracellular AMP-to-ATP ratio and plays a central role cellular responses to metabolic stress. Although activation of AMPK has been shown have anti-inflammatory effects, there little information concerning that may play modulating neutrophil function neutrophil-dependent inflammatory events, such as acute lung injury. To examine these issues, we determined effects pharmacological activators AMPK,...
Idiopathic pulmonary fibrosis (IPF) is a disease with relentless course and limited therapeutic options. Nintedanib (BIBF-1120) multiple tyrosine kinase inhibitor recently approved by the U.S. Food Drug Administration for treatment of IPF. The precise antifibrotic mechanism(s) action nintedanib, however, not known. Therefore, we studied effects nintedanib on fibroblasts isolated from lungs patients Protein gene expression profibrotic markers were assessed Western immunoblotting real-time...
Exaggerated release of neutrophil extracellular traps (NETs) along with decreased NET clearance and inability to remove apoptotic cells (efferocytosis) may contribute sustained inflammation in acute respiratory distress syndrome (ARDS). Recent studies experimental models ARDS have revealed the crosstalk between AMP-activated protein kinase (AMPK) high-mobility group box 1 (HMGB1), which effectiveness efferocytosis, thereby reducing severity.We investigated by macrophages from control...
Glycogen synthase kinase-3β (GSK3β) is a central figure in Wnt signaling, which its activity controlled by regulatory binding proteins. Here we show that proteins outside the pathway also control of GSK3β. DNA damage induced camptothecin, activates tumor suppressor p53, was found to activate This activation occurred phosphorylation-independent mechanism involving direct GSK3β confined nucleus where p53 localized, and mutated (R175H) bound but did not Activation GSK3 promoted responses...
Contraction is crucial in maintaining the differentiated phenotype of myofibroblasts. an energy-dependent mechanism that relies on production ATP by mitochondria and/or glycolysis. Although role mitochondrial biogenesis adaptive responses skeletal muscle to exercise well appreciated, mechanisms governing energetic adaptation myofibroblasts are not understood. Our study demonstrates induction and aerobic glycolysis response differentiation-inducing factor transforming growth β1 (TGF-β1). This...
Although AMPK plays well-established roles in the modulation of energy balance, recent studies have shown that activation has potent anti-inflammatory effects. In present experiments, we examined role phagocytosis. We found ingestion Escherichia coli or apoptotic cells by macrophages increased activity. ability neutrophils to ingest bacteria (by 46±7.8 85±26%, respectively, compared control, P<0.05) and 21±1.4%, P<0.05 control). resulted cytoskeletal reorganization, including enhanced...
Acute lung injury (ALI) is characterized by exuberant proinflammatory responses and mitochondrial dysfunction. However, the link between dysfunction inflammation in ALI not well understood. In this report, we demonstrate a critical role for NAD+-dependent deacetylase, sirtuin-3 (SIRT3), regulating macrophage bioenergetics, ROS formation, responses. We found that SIRT3 expression was significantly diminished lungs of mice subjected to LPS-induced ALI. SIRT3-deficient (SIRT3-/-) develop more...
Rationale: Cigarette smoke (CS) inhalation triggers oxidative stress and inflammation, leading to accelerated lung aging, apoptosis, emphysema, as well systemic pathologies. Metformin is beneficial for protecting against aging-related diseases. Objectives: We sought investigate whether metformin may ameliorate CS-induced pathologies of emphysematous chronic obstructive pulmonary disease (COPD). Methods: Mice were exposed chronically CS fed metformin-enriched chow the second half exposure....
mTOR complex 1 (mTORC1) plays a central role in cell growth and cellular responses to metabolic stress. Although mTORC1 has been shown be activated after Toll-like receptor (TLR)-4 engagement, there is little information concerning the that may play modulating neutrophil function neutrophil-dependent inflammatory events, such as acute lung injury. To examine these issues, we determined effects of rapamycin-induced inhibition on TLR2- TLR4-induced activation. was dose- time-dependently murine...
Phagocytosis of apoptotic cells, also called efferocytosis, is an essential feature immune responses and critical for the resolution inflammation. Plasma tissue levels plasminogen activator inhibitor-1 (PAI-1), inhibitor fibrinolysis, are elevated in inflammatory conditions, including sepsis acute lung injury, which activated neutrophils accumulate tissues contribute to organ dysfunction. In this study, we explored potential involvement PAI-1 modulating neutrophil efferocytosis. We found...
Although reactive oxygen species (ROS) are generally considered to be proinflammatory and contribute cellular organ dysfunction when present in excessive amounts, there is evidence that specific ROS, particularly hydrogen peroxide (H(2)O(2)), may have antiinflammatory properties.To address the role increases intracellular H(2)O(2) play acute inflammatory processes, we examined effects of catalase inhibition or absence on LPS-induced responses.Neutrophils from control acatalasemic mice,...
Although resistin was recently found to modulate insulin resistance in preclinical models of type II diabetes and obesity, recent studies also suggested that has proinflammatory properties. We examined whether the human-specific variant affects neutrophil activation severity LPS-induced acute lung injury. Because human mouse have distinct patterns tissue distribution, experiments were performed using humanized mice exclusively express (hRTN(+/-)(/-)) but are deficient resistin. Enhanced...
Abstract An inability of neutrophils to eliminate invading microorganisms is frequently associated with severe infection and may contribute the high mortality rates sepsis. In present studies, we examined whether metformin other 5′ adenosine monophosphate-activated protein kinase (AMPK) activators affect neutrophil motility, phagocytosis bacterial killing. We found that activation AMPK enhanced chemotaxis in vitro vivo , also counteracted inhibition induced by exposure lipopolysaccharide...
Abstract Chemoresistance due to heterogeneity of the tumor microenvironment (TME) hampers long-term efficacy first-line therapies for lung cancer. Current combination cancer provide only modest improvement in survival, implicating necessity novel approaches that suppress malignant growth and stimulate antitumor immunity. Oxidative stress TME promotes immunosuppression by tumor-infiltrating myeloid-derived suppressor cells (MDSC), which inhibit host protective Using a murine model cancer, we...
Although AMP-activated protein kinase (AMPK) is involved in regulating carbohydrate and lipid metabolism, activated AMPK also plays an anti-inflammatory role many cell populations. However, despite the ability of activation to diminish severity inflammatory responses, previous studies have found that activity diminished LPS-treated neutrophils lungs mice with LPS-induced acute lung injury (ALI). Since GSK3β participates activity, we examined potential roles for modulating macrophages...
Indoleamine 2,3-dioxygenase (IDO) has been implicated in immune evasion by tumors. Upregulation of this tryptophan (Trp)-catabolizing enzyme, tumor cells and myeloid-derived suppressor (MDSCs) within the microenvironment (TME), leads to Trp depletion that impairs cytotoxic T cell responses survival; however, exact mechanisms remain incompletely understood. We previously reported a combination therapy gemcitabine superoxide dismutase mimetic promotes anti-tumor immunity mouse model lung...
Acute lung injury secondary to sepsis is a leading cause of mortality in sepsis-related death. Present therapies are not effective reversing endothelial cell dysfunction, which plays key role increased vascular permeability and compromised function. AMP-activated protein kinase (AMPK) molecular sensor important for detection mediation cellular adaptations disruptive stimuli. In this study, we sought determine the AMPK resolving sepsis-injured lung. function was determined vivo using rat...
Matricellular proteins mediate pleiotropic effects during tissue injury and repair. CCN1 is a matricellular protein that has been implicated in angiogenesis, inflammation, wound In this study, we identified as gene differentially up-regulated alveolar mesenchymal cells of human subjects with rapidly progressive idiopathic pulmonary fibrosis (IPF). Elevated levels mRNA were confirmed lung tissues IPF undergoing transplantation, was predominantly localized to fibroblastic foci. expression ex...