scholarly journals Upregulation of TLR1, TLR2, TLR4, and IRAK-2 Expression During ML-1 Cell Differentiation to Macrophages: Role in the Potentiation of Cellular Responses to LPS and LTA

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Kassim Traore ◽  
Barry Zirkin ◽  
Rajesh K. Thimmulappa ◽  
Shyam Biswal ◽  
Michael A. Trush
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Cell Differentiation ◽  
Inflammatory Cytokines ◽  
Cellular Responses ◽  
Signaling Cascade ◽  
Oxygen Species ◽  
Induced Differentiation ◽  
Protein Levels

12-O-tetradecanoylphorbol 13-acetate (TPA) induces the differentiation of human myeloid ML-1 cells to macrophages. In the current study, the expression, responsiveness, and regulation of toll-like receptors (TLRs) in TPA-induced ML-1-derived macrophages were investigated. We have found that TPA-induced differentiation of ML-1 cells was accompanied by the upregulation of TLR1, TLR2, TLR4, and CD14 expression at both the mRNA and protein levels. Interestingly, TLR1 and TLR4 protein expression on ML-1 cells could be blocked by pretreatment with U0126, suggesting the role of an Erk1/2-induced differentiation signal in this process. In addition, the expression of IRAK-2, a key member of the TLR/IRAK-2/NF-κB-dependent signaling cascade was also induced in response to TPA. Accordingly, we demonstrated an increased cellular release of inflammatory cytokines (TNF-α and various interleukins) upon stimulation with LPS and LTA ligands for TLR4 and TLR2, respectively. Furthermore, using luminol-dependent chemiluminescence, addition of LPS and LTA induces a sustained DPI-inhibitable generation of reactive oxygen species (ROS) by the differentiated ML-1 cells. Together, these data suggest that the increase in the responsiveness of TPA-treated ML-1 cells to LPS and LTA occurs in response to the upregulation of their respective receptors as well as an induction of the IRAK-2 gene expression.

The role of chloroplasts in plant pathology

2017 ◽  
Vol 62 (1) ◽  
pp. 21-39 ◽  
Author(s):  
Robert G. Sowden ◽  
Samuel J. Watson ◽  
Paul Jarvis
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Abiotic Stress Tolerance ◽  
Oxygen Species ◽  
Host Gene Expression ◽  
Host Proteins ◽  
Abiotic And Biotic Stresses ◽  
Biotic Stresses ◽  
Chloroplast Proteome

Plants have evolved complex tolerance systems to survive abiotic and biotic stresses. Central to these programmes is a sophisticated conversation of signals between the chloroplast and the nucleus. In this review, we examine the antagonism between abiotic stress tolerance (AST) and immunity: we propose that to generate immunogenic signals, plants must disable AST systems, in particular those that manage reactive oxygen species (ROS), while the pathogen seeks to reactivate or enhance those systems to achieve virulence. By boosting host systems of AST, pathogens trick the plant into suppressing chloroplast immunogenic signals and steer the host into making an inappropriate immune response. Pathogens disrupt chloroplast function, both transcriptionally—by secreting effectors that alter host gene expression by interacting with defence-related kinase cascades, with transcription factors, or with promoters themselves—and post-transcriptionally, by delivering effectors that enter the chloroplast or alter the localization of host proteins to change chloroplast activities. These mechanisms reconfigure the chloroplast proteome and chloroplast-originating immunogenic signals in order to promote infection.

Oxidative Stress and Cancer

2019 ◽  
Vol 24 (40) ◽  
pp. 4771-4778 ◽  
Author(s):  
James E. Klaunig
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Cell Proliferation ◽  
Dna Repair ◽  
Oxidative Damage ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Genetic Inheritance

Background: Cancer is considered a major cause of death worldwide. The etiology of cancer is linked to environmental and genetic inheritance causes. Approximately 90 percent of all human cancers have an environmental cause (non-genetic inheritance) predominantly through lifestyle choices (smoking, diet, UV radiation) while the remaining due to infections and chemical exposure. Cancer is a multistage process that involves mutational changes and uncontrolled cell proliferation. Research has firmly established a causal and contributory role of oxidative stress and oxidative damage in cancer initiation and progression. Methods: The purpose of this article is to review the role that oxidative stress and reactive oxygen species play in the development of cancer. Both endogenous and exogenous sources of reactive oxygen species result in increased oxidative stress in the cell. Excess reactive oxygen fumed can result in damage to and modification of cellular macromolecules most importantly genomic DNA that can produce mutations. In addition, oxidative stress modulates gene expression of downstream targets involved in DNA repair, cell proliferation and antioxidants. The modulation of gene expression by oxidative stress occurs in part through activation or inhibition of transcription factors and second messengers. The role of single nuclear polymorphism for oxidative DNA repair and enzymatic antioxidants is important in determining the potential human cancer risk. Conclusion: oxidative stress and the resulting oxidative damage are important contributors to the formation and progression of cancer.

scholarly journals CD157 Confers Host Resistance to Mycobacterium tuberculosis via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Qianting Yang ◽  
Mingfeng Liao ◽  
Wenfei Wang ◽  
Mingxia Zhang ◽  
Qi Chen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mycobacterium Tuberculosis ◽  
Host Resistance ◽  
Ros Production ◽  
Oxygen Species ◽  
Effective Strategy ◽  
Content Type ◽  
Protein Levels

ABSTRACT Recruitment of monocytes to the infection site is critical for host resistance against Mycobacterium tuberculosis. CD157 has a crucial role in neutrophil and monocyte transendothelial migration and adhesion, but its role in tuberculosis (TB) is unclear. Here, we show that both mRNA and protein levels of Cd157 are significantly increased during M. tuberculosis infection. Deficiency of Cd157 impaired host response to M. tuberculosis infection by increasing bacterial burden and inflammation in the lung in the murine TB model. In vitro experiments show that the bactericidal ability was compromised in Cd157 knockout (KO) macrophages, which was due to impaired M. tuberculosis-induced reactive oxygen species (ROS) production. We further reveal that CD157 interacts with TLR2 and PKCzeta and facilitates M. tuberculosis-induced ROS production in Cd157 KO macrophages, which resulted in enhanced M. tuberculosis killing. For the clinic aspect, we observe that the expression of CD157 decreases after effective anti-TB chemotherapy. CD157 is specifically increased in pleural fluid in tuberculous pleurisy patients compared to pneumonia and lung cancer patients. Interestingly, the levels of soluble CD157 (sCD157) correlate with human peripheral monocyte-derived macrophage bactericidal activity. Exogenous application of sCD157 could compensate for macrophage bactericidal ability and restore ROS production. In conclusion, we have identified a novel protective immune function of CD157 during M. tuberculosis infection via TLR2-dependent ROS production. Application of sCD157 might be an effective strategy for host-directed therapy against TB in those with insufficient CD157 production. IMPORTANCE Tuberculosis, a chronic bacterial disease caused by Mycobacterium tuberculosis, remains a major global health problem. CD157, a dual-function receptor and β-NAD+-metabolizing ectoenzyme, promotes cell polarization, regulates chemotaxis induced through the high-affinity fMLP receptor, and controls transendothelial migration. The role of CD157 in TB pathogenesis remains unknown. In this study, we find that both mRNA and protein levels of CD157 are significantly increased in TB. Deficiency of CD157 impaired host defense against M. tuberculosis infection both in vivo and in vitro, which is mediated by an interaction among CD157, TLR2, and PKCzeta. This interaction facilitates M. tuberculosis-induced macrophagic ROS production, which enhances macrophage bactericidal activity. Interestingly, the sCD157 level in plasma is reversibly associated with MDM M. tuberculosis killing activity. By uncovering the role of CD157 in pathogenesis of TB for the first time, our work demonstrated that application of soluble CD157 might be an effective strategy for host-directed therapy against TB.

scholarly journals RasGAP Promotes Autophagy and Thereby Suppresses Platelet-Derived Growth Factor Receptor-Mediated Signaling Events, Cellular Responses, and Pathology

2015 ◽  
Vol 35 (10) ◽  
pp. 1673-1685 ◽  
Author(s):  
Hetian Lei ◽  
Cynthia X. Qian ◽  
Jinghu Lei ◽  
Luis J. Haddock ◽  
Shizuo Mukai ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factor Receptor ◽  
Cellular Responses ◽  
Underlying Mechanism ◽  
Platelet Derived Growth Factor ◽  
Eye Disease ◽  
Oxygen Species ◽  
Gtpase Activating Protein ◽  
Indirect Activation

Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) make profound contributions to both physiology and pathology. While it is widely believed that direct (PDGF-mediated) activation is the primary mode of activating PDGFRs, the discovery that they can also be activated indirectly begs the question of the relevance of the indirect mode of activating PDGFRs. In the context of a blinding eye disease, indirect activation of PDGFRα results in persistent signaling, which suppresses the level of p53 and thereby promotes viability of cells that drive pathogenesis. Under the same conditions, PDGFRβ fails to undergo indirect activation. In this paper, we report that RasGAP (GTPase-activating protein of Ras) prevented indirect activation of PDGFRβ. RasGAP, which associates with PDGFRβ but not PDGFRα, reduced the level of mitochondrion-derived reactive oxygen species, which are required for enduring activation of PDGFRs. Furthermore, preventing PDGFRβ from associating with RasGAP allowed it to signal enduringly and drive pathogenesis of a blinding eye disease. These results indicate a previously unappreciated role of RasGAP in antagonizing indirect activation of PDGFRβ, define the underlying mechanism, and raise the possibility that PDGFRβ-mediated diseases involve indirect activation of PDGFRβ.

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