Role of Fas–FasL in inflammatory diseases

2001 ◽  
Vol 3 (31) ◽  
pp. 1-18 ◽  
Author(s):  
Joe O'Connell
Keyword(s):  
Fas Ligand ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Inflammatory Reactions ◽  
Immune Effector ◽  
Effector Cells ◽  
Therapeutic Goals ◽  
Cytokines And Chemokines ◽  
Apoptosis And Inflammation

Fas ligand (FasL) induces programmed cell death, or ‘apoptosis’, in cells expressing its cognate receptor, Fas (CD95/APO-1). There is evidence that FasL precludes inflammatory reactions from sites of ‘immune privilege’ by triggering Fas-mediated apoptosis of infiltrating pro-inflammatory cells. The ability of FasL to impair immune responses is being pursued as a possible means of protecting tissue transplants from immunological rejection, and therapeutic promise has been reported in some experiments. However, FasL is becoming an enigmatic molecule, exhibiting pro-inflammatory activity independently of its ability to mediate immune downregulation. FasL can recruit and activate neutrophils and macrophages in some experimental situations. Triggering of Fas in some cell types has been shown to upregulate expression of certain pro-inflammatory cytokines and chemokines, providing an unexpected link between apoptosis and inflammation. FasL appears to contribute to the destruction of Fas-sensitive end-organ cells during inflammation. This appears to occur in two ways: (1) direct killing by cytotoxic immune effector cells expressing FasL; or (2) autocrine cell suicide of end-organ cells that upregulate their own FasL in the inflammatory context. Depending on the condition, or the site of inflammation, either or both mechanisms may occur. Prevention of Fas-mediated end-organ apoptosis and enhancement of Fas-mediated apoptosis of inflammatory cells are emerging as potential anti-inflammatory therapeutic goals.

scholarly journals Indian Medicinal Plants and Formulations and Their Potential Against COVID-19–Preclinical and Clinical Research

2021 ◽  
Vol 11 ◽  
Author(s):  
Sayeed Ahmad ◽  
Sultan Zahiruddin ◽  
Bushra Parveen ◽  
Parakh Basist ◽  
Abida Parveen ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Rural Areas ◽  
Case Fatality ◽  
Current Crisis ◽  
Inflammatory Reactions ◽  
Immune Effector ◽  
Effector Cells ◽  
Traditional Medicines ◽  
Cytokines And Chemokines ◽  
Indian Medicinal Plants

The cases of COVID-19 are still increasing day-by-day worldwide, even after a year of its first occurrence in Wuhan city of China. The spreading of SARS-CoV-2 infection is very fast and different from other SARS-CoV infections possibly due to structural differences in S proteins. The patients with severe diseases may die due to acute respiratory distress syndrome (ARDS) caused by systemic inflammatory reactions due to the excessive release of pro-inflammatory cytokines and chemokines by the immune effector cells. In India too, it is spreading very rapidly, although the case fatality rate is below 1.50% (https://www.statista.com), which is markedly less than in other countries, despite the dense population and minimal health infrastructure in rural areas. This may be due to the routine use of many immunomodulator medicinal plants and traditional AYUSH formulations by the Indian people. This communication reviews the AYUSH recommended formulations and their ingredients, routinely used medicinal plants and formulations by Indian population as well as other promising Indian medicinal plants, which can be tested against COVID-19. Special emphasis is placed on Indian medicinal plants reported for antiviral, immunomodulatory and anti-allergic/anti-inflammatory activities and they are categorized for prioritization in research on the basis of earlier reports. The traditional AYUSH medicines currently under clinical trials against COVID-19 are also discussed as well as furtherance of pre-clinical and clinical testing of the potential traditional medicines against COVID-19 and SARS-CoV-2. The results of the clinical studies on AYUSH drugs will guide the policymakers from the AYUSH systems of medicines to maneuver their policies for public health, provide information to the global scientific community and could form a platform for collaborative studies at national and global levels. It is thereby suggested that promising AYUSH formulations and Indian medicinal plants must be investigated on a priority basis to solve the current crisis.

scholarly journals Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models

2021 ◽  
Vol 22 (4) ◽  
pp. 1514 ◽  
Author(s):  
Akihiro Yachie
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Heme Oxygenase ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Pharmacological Intervention ◽  
Heme Oxygenase 1 ◽  
Inflammatory Reactions

Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.

scholarly journals Mutations in the Fas Antigen in Patients With Multiple Myeloma

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4266-4270 ◽  
Author(s):  
Terry H. Landowski ◽  
Ning Qu ◽  
Ibrahim Buyuksal ◽  
Jeffrey S. Painter ◽  
William S. Dalton
Keyword(s):  
Multiple Myeloma ◽  
Fas Ligand ◽  
Genetic Defect ◽  
Point Mutations ◽  
Neoplastic Disease ◽  
Loss Of Function ◽  
Fas Antigen ◽  
Immune Effector ◽  
Effector Cells ◽  
A Site

Programmed cell death, or apoptosis, is well documented as a physiological means of eliminating activated lymphocytes and maintaining immune homeostasis. Apoptosis has also been implicated in the targeting of tumor cells by cytotoxic T lymphocytes and natural killer cells. One of the two primary mechanisms used in cell-mediated cytotoxicity is the Fas/FasLigand system. Activated or transformed cells expressing the Fas antigen on their surface are susceptible to killing by immune effector cells that express the Fas ligand. Many neoplastic cells, including those derived from patients with multiple myeloma, express Fas antigen on their surface, but do not undergo apoptosis in response to antigen crosslinking. One possibility for the lack of Fas-mediated apoptosis includes mutations in the Fas antigen. Loss of function mutations in the Fas antigen have been associated with congenital autoimmune disease in humans, and have been defined as the genetic defect the in lpr mice. Mutations in the Fas antigen have not been previously described in cancer patients. In this study, we show that mutations occur in the Fas antigen which may cause loss of function and contribute to the pathogenesis of the neoplastic disease, multiple myeloma. Using reverse transcriptase-polymerase chain reaction (RT-PCR), single-stranded conformation polymorphism (SSCP) analysis, and DNA sequencing, we examined the cDNA structure of the Fas antigen in 54 bone marrow (BM) specimens obtained from myeloma patients. Six patient specimens (11%) did not express detectable levels of Fas antigen mRNA. Of the 48 BM specimens which did express Fas antigen, 5 (10%) displayed point mutations. All of the mutations identified were located in the cytoplasmic region of the Fas antigen known to be involved in transduction of an apoptotic signal. Two separate individuals demonstrated an identical mutation at a site previously shown to be mutated in the congenital autoimmune syndrome, ALPS. One patient exhibited a point mutation at a site only two amino acids removed from the documented lesion of the lprcg mouse. Although the functional status of these point mutations remains to be determined, we propose that Fas antigen mutations may contribute to the pathogenesis and progression of myeloma in some patients.

scholarly journals Mutations in the Fas Antigen in Patients With Multiple Myeloma

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4266-4270 ◽  
Author(s):  
Terry H. Landowski ◽  
Ning Qu ◽  
Ibrahim Buyuksal ◽  
Jeffrey S. Painter ◽  
William S. Dalton
Keyword(s):  
Multiple Myeloma ◽  
Fas Ligand ◽  
Genetic Defect ◽  
Point Mutations ◽  
Neoplastic Disease ◽  
Loss Of Function ◽  
Fas Antigen ◽  
Immune Effector ◽  
Effector Cells ◽  
A Site

Abstract Programmed cell death, or apoptosis, is well documented as a physiological means of eliminating activated lymphocytes and maintaining immune homeostasis. Apoptosis has also been implicated in the targeting of tumor cells by cytotoxic T lymphocytes and natural killer cells. One of the two primary mechanisms used in cell-mediated cytotoxicity is the Fas/FasLigand system. Activated or transformed cells expressing the Fas antigen on their surface are susceptible to killing by immune effector cells that express the Fas ligand. Many neoplastic cells, including those derived from patients with multiple myeloma, express Fas antigen on their surface, but do not undergo apoptosis in response to antigen crosslinking. One possibility for the lack of Fas-mediated apoptosis includes mutations in the Fas antigen. Loss of function mutations in the Fas antigen have been associated with congenital autoimmune disease in humans, and have been defined as the genetic defect the in lpr mice. Mutations in the Fas antigen have not been previously described in cancer patients. In this study, we show that mutations occur in the Fas antigen which may cause loss of function and contribute to the pathogenesis of the neoplastic disease, multiple myeloma. Using reverse transcriptase-polymerase chain reaction (RT-PCR), single-stranded conformation polymorphism (SSCP) analysis, and DNA sequencing, we examined the cDNA structure of the Fas antigen in 54 bone marrow (BM) specimens obtained from myeloma patients. Six patient specimens (11%) did not express detectable levels of Fas antigen mRNA. Of the 48 BM specimens which did express Fas antigen, 5 (10%) displayed point mutations. All of the mutations identified were located in the cytoplasmic region of the Fas antigen known to be involved in transduction of an apoptotic signal. Two separate individuals demonstrated an identical mutation at a site previously shown to be mutated in the congenital autoimmune syndrome, ALPS. One patient exhibited a point mutation at a site only two amino acids removed from the documented lesion of the lprcg mouse. Although the functional status of these point mutations remains to be determined, we propose that Fas antigen mutations may contribute to the pathogenesis and progression of myeloma in some patients.

scholarly journals High Levels of CXCL10 Are Produced by Intestinal Epithelial Cells in AIDS Patients with Active Cryptosporidiosis but Not after Reconstitution of Immunity

2006 ◽  
Vol 75 (1) ◽  
pp. 481-487 ◽  
Author(s):  
Heuy-Ching Wang ◽  
Sara M. Dann ◽  
Pablo C. Okhuysen ◽  
Dorothy E. Lewis ◽  
Cynthia L. Chappell ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Pearson Correlation ◽  
Parasite Burden ◽  
Inflammatory Cells ◽  
Aids Patients ◽  
Monocyte Chemoattractant Protein 1 ◽  
Immune Effector ◽  
Effector Cells ◽  
Normal Volunteers ◽  
Few Data

ABSTRACT Chemokines play key roles in attracting immune cells to sites of infections. However, few data on chemokine expression in the gut during human infections are available. We examined expression of chemokines in intestinal tissues of AIDS patients during active Cryptosporidium infection and during resolution of such an infection. The chemokines and cytokines in cell lysates from jejunal biopsy tissues were assayed by a 22-multiplex bead immunoassay. CXCL10 (IP-10) and its receptor, CXCR3, in sections were studied by immunohistochemistry. In biopsies from AIDS patients with active cryptosporidiosis, four chemokines (CXCL10, CCL11 [eotaxin], CCL5 [RANTES], and CCL2 [monocyte chemoattractant protein 1]) and three cytokines (interleukin-1α [IL-1α], IL-10, and granulocyte colony-stimulating factor) were detected. The level of CXCL10 was significantly increased in AIDS patients with cryptosporidiosis compared to the level in AIDS patients without cryptosporidiosis or in normal volunteers (median in AIDS patients with cryptosporidiosis, 508 pg/mg protein, compared to 111 pg/mg and 72 pg/mg protein in AIDS patients without cryptosporidiosis and in normal volunteers, respectively [P < 0.05 and P < 0.005, respectively, as determined by a Mann-Whitney test]). The level of CXCL10 correlated with the parasite burden (as measured by the number of Cryptosporidium oocysts in the stools) and also with the IL-1α concentration (Pearson correlation values, 0.961 [P < 0.01] and 0.737 [P < 0.05]). As determined by immunohistochemistry, CXCL10 localized to epithelial cells at the site of infection. Following effective antiparasite and antiretroviral therapy, Cryptosporidium infections resolved, and the levels of CXCL10 decreased to normal levels. We hypothesized that CXCL10 plays an important role in the resolution of cryptosporidiosis by attracting immune effector cells to the site of infection. By contrast, in AIDS patients lacking effector cells, CXCL10 may contribute to the immunopathogenesis by recruiting inflammatory cells.

Immune Regulatory Properties Are a Common Feature Of Stem Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5419-5419
Author(s):  
Mariano Di Trapani ◽  
Giulio Bassi ◽  
Mario Ricciardi ◽  
Emanuela Fontana ◽  
Francesco Bifari ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Immune Regulation ◽  
Cell Activation ◽  
Conflicts Of Interest ◽  
Inflammatory Diseases ◽  
Activation Markers ◽  
Immune Effector ◽  
Effector Cells ◽  
Cell Based Therapy

Abstract Allogeneic stem cell-based therapy is a promising tool for the treatment of a range of human degenerative and inflammatory diseases. Many reports highlighted the immune modulatory properties of some stem cell (SC) types, such as mesenchymal stromal cells (MSCs), but a comparative study with SCs of different origin, to assess whether immune regulation is a general SC property, is still lacking. To this aim, we applied highly standardized methods employed for MSC characterization to compare the immunological properties of bone marrow-MSCs, olfactory ecto-mesenchymal stem cells, leptomeningeal stem cells, and three different c-Kit-positive SC types, i.e. amniotic fluid SCs, cardiac SCs, and lung SCs. We found that all the analyzed human SCs share a common pattern of immunological features, in terms of expression of activation markers, modulatory activity towards immune effector cells, immunogenicity and molecular inhibitory pathways, with some SC type-related peculiarities. In addition, we found that the inhibitory behaviour is not a constitutive property of SCs, but is acquired as a consequence of immune effector cell activation, as previously described for MSCs. Thus, immune regulation is a general property of stem cells and the characterization of this phenomenon may be useful for a proper therapeutical use of SCs. Disclosures: No relevant conflicts of interest to declare.

Glutathione peroxidase activity in blood cells from aspirin-induced asthma patients

2003 ◽  
Vol 40 (4) ◽  
pp. 369-373 ◽  
Author(s):  
A. M. Hassan
Keyword(s):  
Arachidonic Acid ◽  
Glutathione Peroxidase ◽  
Blood Cells ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Peripheral Blood Lymphocytes ◽  
Effector Cells ◽  
Asthma Patients ◽  
Hydroperoxyeicosatetraenoic Acid ◽  
Gpx Activity

Aspirin and other inhibitors of cyclo-oxygenase precipitate acute bronchospasm in about 10% of adult asthmatics. It has been assumed that cyclo-oxygenase is involved in the pathogenesis of bronchospasm, but the precise mechanism remains poorly understood. The oxygenation products of arachidonic acid include hydroperoxyeicosatetraenoic acid and cyclic endoperoxides. Glutathione peroxidase (GPX) reduces semi-stable hydroperoxides to less reactive alcohols and removes H2O2 involved in inflammation. GPX could, therefore, modulate oxidation of arachidonic acid in the cyclo-oxygenase and lipoxygenase pathways, but the involvement of GPX in the pathogenesis of asthma has received little attention. We measured GPX activity in platelets, peripheral blood lymphocytes (PBL), red blood cells (RBC) and plasma from 13 patients with aspirin-induced asthma (AIA). Age- and sex-matched healthy individuals served as the comparison group. The patients had significantly higher GPX activity in platelets (P = 0·05) and tended to have high GPX activity (P = 0·08) in plasma but not in RBC or PBL. The results suggest that the increased GPX activity may be an adaptive advantage in AIA to protect against increased free radical production by inflammatory cells. That the higher GPX activity was not evident in all cell types studied may indicate a differential role played by them as effector cells in the pathogenesis of AIA.

scholarly journals Is the cellular response to cigarette smoke predictive of the phenotypic variation of COPD?

2011 ◽  
Vol 300 (6) ◽  
pp. L809-L810 ◽  
Author(s):  
Gye Young Park ◽  
John W. Christman
Keyword(s):  
Cigarette Smoking ◽  
Phenotypic Variation ◽  
Cellular Response ◽  
Vascular Diseases ◽  
Cell Types ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Immune Effector ◽  
Effector Cells ◽  
Organ Systems

the adverse health consequences of cigarette smoking are not limited to the lung but also include effects on multiple other organ systems that are exposed directly or indirectly to the hazardous gaseous and soluble compounds generated by burning tobacco. Cigarette smoking (CS) is a risk factor for many major diseases including chronic obstructive pulmonary disease (COPD), atherosclerosis, cerebral and coronary vascular diseases, hypertension, and many types of cancer. Within the diagnosis category of COPD, it is widely recognized that there is substantial phenotypic heterogeneity with respect to both pulmonary and extrapulmonary manifestations. To understand the variability in responses to CS, it becomes essential to decipher the involved mechanisms at a cellular and molecular level that contribute to cigarette-related pathology. In this issue of the Journal, there are three papers ( 1 , 4 , 6 ) that provide insight regarding the molecular pathogenesis of CS-related COPD that could be related to phenotypic variation, by examining three classes of cell types of lung: endothelial cells, epithelial cells, and immune effector cells.

scholarly journals Peroxisome Proliferator–activated Receptors α and γ Down-regulate Allergic Inflammation and Eosinophil Activation

2003 ◽  
Vol 198 (3) ◽  
pp. 411-421 ◽  
Author(s):  
Gaetane Woerly ◽  
Kohei Honda ◽  
Marc Loyens ◽  
Jean-Paul Papin ◽  
Johan Auwerx ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Allergic Inflammation ◽  
Serum Levels ◽  
Cell Types ◽  
Specific Ige ◽  
Peroxisome Proliferator ◽  
Inflammatory Reactions ◽  
Effector Cells ◽  
Peroxisome Proliferator Activated Receptors

Allergic asthma is characterized by airway hyperresponsiveness, eosinophilia, and mucus accumulation and is associated with increased IgE concentrations. We demonstrate here that peroxisome proliferator–activated receptors (PPARs), PPAR-α and PPAR-γ, which have been shown recently to be involved in the regulation of various cell types within the immune system, decrease antigen-induced airway hyperresponsiveness, lung inflammation, eosinophilia, cytokine production, and GATA-3 expression as well as serum levels of antigen-specific IgE in a murine model of human asthma. In addition, we demonstrate that PPAR-α and -γ are expressed in eosinophils and their activation inhibits in vitro chemotaxis and antibody-dependent cellular cytotoxicity. Thus, PPAR-α and -γ (co)agonists might be of therapeutic interest for the regulation of allergic or inflammatory reactions by targeting both regulatory and effector cells involved in the immune response.

Cellular Infiltration in Allergic Late-Phase Reaction of the Nose: Immunohistochemical Studies

1991 ◽  
Vol 5 (6) ◽  
pp. 227-234 ◽  
Author(s):  
Claus Bachert ◽  
Gerhard Schindelbeck ◽  
Ulrich Hauser
Keyword(s):  
Antigen Processing ◽  
Late Phase ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Allergen Exposure ◽  
Mucosal Surface ◽  
Eosinophil Infiltration ◽  
Phase Reaction ◽  
Inflammatory Reactions ◽  
Late Phase Reaction

As with the bronchial system and the skin, the human nose may react with an immediate-phase (IPR) and late-phase reaction (LPR) upon allergen exposure. In this study we challenged intranasally 11 unselected grass-pollen-allergic patients and three normal controls with increasing allergen concentrations to provoke similar IPR symptoms in each person. A nasal symptom score and the bilateral nasal resistance were measured for 8 hours, repeated mucosal surface cell samples were performed (brush technique) before and every 2 hours after the challenge for histological and immunohistochemical investigations on cellular events during the nasal LPR. Apart from neutrophil and eosinophil infiltration, the LPR was accompanied by the migration of metachromatic cells, IgE positive cells, and macrophages/monocyte-like cells. IgE-positive cells could be identified as mast cells/basophils; from the discrepancy between the numbers of IgE- and metachromatic cell types we conclude the degranulation of these mediator cells not only during the IPR, but also during the LPR. The migration of IGE-bearing mediator cells onto the mucosal surface may represent an explanation for the increased reactivity of the organ due to repeated allergen exposure. Furthermore, the migration points to these cells as a means of transport for IgE molecules. The increase in density of macrophages/monocyte-like cells on the nasal mucosal surface during the LPR suggests an important role of these inflammatory cells in antigen processing and/or maintaining of chronic inflammatory reactions.

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