scholarly journals Macrophage-Targeted Photodynamic Therapy: Scavenger Receptor Expression and Activation State

2005 ◽  
Vol 18 (3) ◽  
pp. 391-402 ◽  
Author(s):  
Q. Liu ◽  
M. R. Hamblin
Keyword(s):  
Photodynamic Therapy ◽  
Cell Lines ◽  
Scavenger Receptor ◽  
Receptor Expression ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Selective Targeting ◽  
Factor Alpha ◽  
Targeted Photodynamic Therapy ◽  
Necrosis Factor

Macrophage-targeted photodynamic therapy (PDT) may have applications in the selective killing of cells involved in atherosclerosis, inflammation and tumor. We have previously shown that a conjugate between the photosensitizer chlorin(e6) (ce6) and maleylated bovine serum albumin (BSA-mal) gives highly selective targeting to macrophages. In this report we examine the effect of macrophage activation and scavenger receptor class A (SRA) expression on this targeting in two murine macrophage tumor cell lines (RAW264.7 and P388D1) and a control murine mammary sarcoma cell line (EMT-6). Cells were pretreated with interferon gamma (IFNγ) and/or lipopolysaccharide (LPS) followed byBSA-ce6-mal addition, and SRA expression, tumor necrosis factor alpha (TNFα) release, conjugate uptake and PDT killing were measured. Both macrophage cell lines expressed SRA and took up conjugate specifically in an SRA-dependent manner, but differences were observed in their response to activation. RAW264.7 expressed increasingly more SRA and took up increasingly more BSA-ce6-mal in response to IFNγ, LPS, and IFNγ+LPS, respectively. The PDT killing did not follow the same pattern as the uptake of the photosensitizer. The increase in uptake in the IFNγ treated cells did not lead to an increase in PDT killing, while stimulation with LPS or IFNγ+LPS resulted in a significant protection against PDT, despite a significant increase in photosensitizer uptake. P388D1 was responsive to neither IFNγ, nor to LPS, or to IFNγ+LPS with respect to SRA expression, conjugate uptake, and PDT killing. These data may have implications for the use of PDT to target physiologically undesirable macrophage subtypes implicated in disease, and on how manipulation of the activation status of the macrophage will influence the PDT effect.

scholarly journals The application of photodynamic therapy in the case of insufficient effect of the inhibitors of tumour necrosis factor in the patients with psoriasis

2016 ◽  
Vol 15 (4) ◽  
pp. 188-190
Author(s):  
E. S Ponich ◽  
E. V Sokolovsky ◽  
Larisa Sergeevna Kruglova
Keyword(s):  
Photodynamic Therapy ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Severity Index ◽  
Chronic Inflammatory Disease ◽  
Tumour Necrosis Factor Alpha ◽  
Photodynamic Treatment ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Psoriasis is a systemic chronic inflammatory disease that affects in the first place the skin and occurs in 1-5% of the general population. The treatment of the patients presenting with this condition implies the application of the topical agent and biological preparations as well as phototherapy and systemic therapy. The patients suffering severe forms of psoriasis in whom systemic immunosuppressive therapy does not yield the desired effect are in need of the treatment with biological preparations. The use of the inhibitors of tumour necrosis factor-alpha produces the insufficient effect even in the case of the positive response, i.e. the psoriasis area and severity index (PASI) of approximately 50 scores (PASI 50). This article presents the results of the application of photodynamic therapy (PDT) for the treatment of 8 patients treated with the inhibitors of tumour necrosis factor-alpha in whom the PASI value of 50 was achieved within the first week after the onset of the treatment. In all these patients, a course of photodynamic therapy consisting of 2-3 procedures made it possible to increase the PASI values to 75 and even 100 scores. It is concluded that the patients showing positive but insufficient effect of biological therapy (PASI 50) need to be prescribed a course of photodynamic treatment in order to enhance the effectiveness of the biological therapeutic factors.

scholarly journals Increased activity and sensitivity of mitochondrial respiratory enzymes to tumor necrosis factor alpha-mediated inhibition is associated with increased cytotoxicity in drug-resistant leukemic cell lines

Blood ◽  
1996 ◽  
Vol 87 (6) ◽  
pp. 2401-2410 ◽  
Author(s):  
L Jia ◽  
SM Kelsey ◽  
MF Grahn ◽  
XR Jiang ◽  
AC Newland
Keyword(s):  
Cell Lines ◽  
Tumor Necrosis ◽  
Leukemic Cell ◽  
Drug Resistant ◽  
Necrosis Factor Alpha ◽  
Leukemic Cell Lines ◽  
Respiratory Inhibition ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Dehydrogenase Complex

The drug-resistant leukemic cell lines, CEM/VLB100 and K/DAU600, are more sensitive to tumor necrosis factor alpha (TNFalpha)-mediated cytotoxicity compared with their parental cell lines, CCRF-CEM and K562 cl.6. Drug-resistant leukemic cell lines have more active mitochondrial function, which is associated with a greater susceptibility to TNFalpha- induced respiratory inhibition. TNFalpha blocked electron transfer at three sites, NADH dehydrogenase (complex I), succinate dehydrogenase (complex II), and cytochrome c oxidase (complex IV). Respiratory rate and electron transport chain enzyme activities were significantly inhibited in the drug-resistant, TNF-sensitive cell lines. Respiratory inhibition preceded cell death by at least 5 to 8 hours. The respiratory failure was not compensated for by appropriate up- regulation of the glycolytic pathway. Increasing mitochondrial respiratory rate and enzyme activities by long-term culture with 2 mmol/L adenosine 5′-diphosphate (ADP) and Pi sensitized both drug- sensitive and drug-resistant cells to TNFalpha-induced cytolysis. Intramitochondrial free radicals generated by paraquat only had a limited and delayed effect on respiratory inhibition and cytolysis in comparison with the effect of TNFalpha. We conclude that TNFalpha- induced cytotoxicity in leukemic cells is, at least in part, mediated by inhibition of mitochondrial respiration. Free radical generation by TNFalpha may not directly lead to the observed inhibition of the mitochondrial electron transport and other mechanisms must be involved.

scholarly journals Chlamydiae Modulate Gamma Interferon, Interleukin-1β, and Tumor Necrosis Factor Alpha Receptor Expression in HeLa Cells

2006 ◽  
Vol 74 (4) ◽  
pp. 2482-2486 ◽  
Author(s):  
Kari Ann Shirey ◽  
Joseph M. Carlin
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Chlamydia Psittaci ◽  
Receptor Expression ◽  
Cytokine Receptors ◽  
Indoleamine Dioxygenase ◽  
Necrosis Factor Alpha ◽  
Synergistic Induction ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Chlamydia psittaci was found to modulate receptor expression for the cytokine receptors that are involved in the synergistic induction of indoleamine dioxygenase in epithelial cells. Increases in receptor expression were seen even with inactivated Chlamydia, suggesting that chlamydial antigens and not products of infection are important for up-regulating cytokine receptor expression.

scholarly journals Bikunin Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Induction in Macrophages

2004 ◽  
Vol 11 (6) ◽  
pp. 1140-1147 ◽  
Author(s):  
Hidenori Matsuzaki ◽  
Hiroshi Kobayashi ◽  
Tatsuo Yagyu ◽  
Kiyoshi Wakahara ◽  
Toshiharu Kondo ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Dose Dependent ◽  
Necrosis Factor

ABSTRACT Bikunin, a Kunitz-type protease inhibitor, exhibits anti-inflammatory activity in protection against cancer and inflammation. To investigate the molecular mechanism of this inhibition, we analyzed the effect of bikunin on tumor necrosis factor alpha (TNF-α) production in human peripheral mononuclear cells stimulated by lipopolysaccharide (LPS), an inflammatory inducer. Here, we show the following results. (i) LPS induced TNF-α expression in time- and dose-dependent manners through phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase pathways. (ii) Bikunin inhibits LPS-induced up-regulation of TNF-α protein expression in a dose-dependent manner, reaching 60% inhibition at the highest doses of bikunin tested (5.0 μM). (iii) Inhibition by bikunin of TNF-α induction correlates with the suppressive capacity of ERK1/2, JNK, and p38 signaling pathways, implicating repressions of at least three different signals in the inhibition. (iv) Bikunin blocks the induction of TNF-α target molecules interleukin-1β (IL-1β) and IL-6 proteins. (v) Bikunin is functional in vivo, and this glycoprotein blocks systemic TNF-α release in mice challenged with LPS. (vi) Finally, bikunin can prevent LPS-induced lethality. In conclusion, bikunin significantly inhibits LPS-induced TNF-α production, suggesting a mechanism of anti-inflammation by bikunin through control of cytokine induction during inflammation. Bikunin might be a candidate for the treatment of inflammation, including septic shock.

scholarly journals Ectodomain Shedding of Preadipocyte Factor 1 (Pref-1) by Tumor Necrosis Factor Alpha Converting Enzyme (TACE) and Inhibition of Adipocyte Differentiation

2006 ◽  
Vol 26 (14) ◽  
pp. 5421-5435 ◽  
Author(s):  
Yuhui Wang ◽  
Hei Sook Sul
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Adipocyte Differentiation ◽  
Soluble Form ◽  
Dependent Manner ◽  
Converting Enzyme ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Preadipocyte factor 1 (Pref-1), an epidermal growth factor repeat containing transmembrane protein found in the preadipocytes, inhibits adipocyte differentiation in vitro and in vivo. Here, we examined the processing of membrane form of Pref-1A to release the 50-kDa soluble form that inhibits adipocyte differentiation. The ectodomain cleavage of Pref-1 is markedly enhanced by phorbol 12-myristate 13-acetate in a dose- and time-dependent manner. The basal and stimulated cleavage is inhibited by the broad metalloproteinase inhibitor GM6001, a fact that suggests that cleavage of membrane Pref-1A is dependent on a metalloproteinase. Next, we showed that release of soluble Pref-1A is inhibited by TAPI-0 and by a tissue inhibitor of metalloproteinase-3, TIMP-3, that can inhibit tumor necrosis factor alpha converting enzyme (TACE), but not by TIMP-1 or TIMP-2. On the other hand, overexpression of TACE increases Pref-1 cleavage to produce the 50-kDa soluble form. Furthermore, this cleavage was not detected in cells with TACE mutation or with TACE small interfering RNA. TACE-mediated shedding of Pref-1 ectodomain inhibits adipocyte differentiation of 3T3-L1 cells and in Pref-1-null mouse embryo fibroblasts transduced with Pref-1A. Identification of TACE as the major protease responsible for conversion of membrane-bound Pref-1 to the biologically active diffusible form provides a new insight into Pref-1 function in adipocyte differentiation.

scholarly journals Resveratrol Modulates Phagocytosis of Bacteria through an NF-κB-Dependent Gene Program

2007 ◽  
Vol 52 (1) ◽  
pp. 121-127 ◽  
Author(s):  
Mitsuhiro Iyori ◽  
Hideo Kataoka ◽  
Haque Mohammad Shamsul ◽  
Kazuto Kiura ◽  
Motoaki Yasuda ◽  
...  
Keyword(s):  
Scavenger Receptor ◽  
Hek293 Cells ◽  
Raw264.7 Cells ◽  
Dependent Manner ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Lectin Receptors ◽  
Macrophage Scavenger Receptor ◽  
Toll Like Receptor 2 ◽  
Factor Alpha

ABSTRACT Many studies have shown that the pharmacological effects of resveratrol, a phytoalexin polyphenolic compound, include protective effects against cancer and inflammation as well as enhancement of stress resistance. In this study, we examined whether resveratrol affected the phagocytosis of bacteria by macrophages and the activation of the transcription factor NF-κB after stimulation with or without the ligand FSL-1 for Toll-like receptor 2 (TLR2). Phagocytosis of Escherichia coli and of Staphylococcus aureus by THP-1 cells and RAW264.7 cells was inhibited by resveratrol in a dose-dependent manner regardless of stimulation with FSL-1. The NF-κB activity in HEK293 cells stably expressing TLR2 was also inhibited by resveratrol after stimulation with FSL-1. Resveratrol also inhibited both the translocation of p65 of NF-κB into nuclei in the transfectant and tumor necrosis factor alpha production by THP-1 cells or RAW264.7 cells. It has recently been reported that TLR-mediated signaling pathways lead to the upregulation of mRNAs of phagocytic receptors, including scavenger receptors and C-type lectin receptors. This study also demonstrated that FSL-1 induced the upregulation of mRNAs of phagocytic receptors such as macrophage scavenger receptor-1, CD36, DC-SIGN, and Dectin-1 and that the FSL-1-induced upregulation of their mRNAs was inhibited by resveratrol. In addition, it was found that the expression of DC-SIGN in HEK293 cells stably expressing DC-SIGN was reduced by resveratrol and that the phagocytic activity was significantly inhibited by resveratrol. Thus, this study suggests that resveratrol inhibited bacterial phagocytosis by macrophages by downregulating the expression of phagocytic receptors and NF-κB activity.

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