Multiplicity of glucocorticoid action in inhibiting allograft rejection

Almawi, WY

doi:10.1016/s0963-6897(98)00042-6

Cited by 32 publications

(29 citation statements)

References 175 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GCs inhibited the expression of proinflammatory and immunoregulatory cytokines, including IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-11, IL-12, IL-15, IL-16, interferon-, tumor necrosis factor-(TNF-), and the colony-stimulating factors (CSF) macrophage (M)-CSF, granulocyte (G)-CSF, CSF-1, and granulocyte-macrophage (GM)-CSF (reviewed in Almawi et al 1996aAlmawi et al , 1998a. Inhibition by GCs of cytokine expression was specific for the GCs, as evidenced by the failure of non-GC steroids to inhibit cytokine expression (Boumpas et al 1993) or T cell proliferation (Almawi et al 1996b), and by the capacity of the GCs receptor (GR) antagonist, RU-486, to abrogate the effects of GCs (Paliogianni & Boumpas 1995, Almawi & Tamim 2001.…”

Section: Glucocorticoid Antiproliferative Effectsmentioning

confidence: 99%

“…Glucocorticoids (GCs) are clinically used in treating disorders of heightened immunity, including transplantation rejection and autoimmunity (Almawi et al 1998a). Despite a vast literature on their effects on T cell activation, the mechanism of action of the GCs remains incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

“…Despite a vast literature on their effects on T cell activation, the mechanism of action of the GCs remains incompletely understood. It is now recognized that their mode of action is multifaceted, since evidence of blockade of T cell immunity by the GCs at several stages in the T cell activation cascade is well documented (Almawi et al 1996a(Almawi et al , 1998a). The major routes by which GCs mediate their effects are many, the most significant of which are inhibition of cytokine production (Kwon et al 1994, Mori et al 1997, Almawi et al 1998a and, for some cytokines, signaling through their high-affinity receptor complex (Paliogianni et al 1993, Monfar & Blenis 1996, Sakai et al 1999, Almawi & Tamim 2001.…”

Section: Introductionmentioning

confidence: 99%

“…It is now recognized that their mode of action is multifaceted, since evidence of blockade of T cell immunity by the GCs at several stages in the T cell activation cascade is well documented (Almawi et al 1996a(Almawi et al , 1998a). The major routes by which GCs mediate their effects are many, the most significant of which are inhibition of cytokine production (Kwon et al 1994, Mori et al 1997, Almawi et al 1998a and, for some cytokines, signaling through their high-affinity receptor complex (Paliogianni et al 1993, Monfar & Blenis 1996, Sakai et al 1999, Almawi & Tamim 2001. Paradoxically, GCs upregulated the expression of some (proinflammatory) high-affinity cytokine receptors on target cells in the face of lost cytokine stimulation (Almawi et al 1998b, Lukiw et al 1999.…”

Section: Introductionmentioning

confidence: 99%

“…Recent evidence suggested an additional mechanism, namely antagonism of transcription factors, in particular nuclear factor-B (NF-B), which resulted in attenuation or arrest of transcriptional activities (Auphan et al 1995, De Bosscher et al 1997. However, it is very likely that GCs may utilize more than one mechanism in exerting their anti-proliferative effect (Almawi et al 1998a). This paper focuses on the effect of GCs on downregulating NF-B activity; for discussion of the effect of GCs on antagonism of other transcription factors the reader is advised to consult excellent reviews published elsewhere (Gottlicher et al 1998, De Bosscher et al 2000a).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Negative regulation of nuclear factor-kappaB activation and function by glucocorticoids

Almawi¹,

Melemedjian²

2002

Journal of Molecular Endocrinology

216

126

View full text Add to dashboard Cite

Glucocorticoids (GCs) exert their anti-inflammatory and antiproliferative effects principally by inhibiting the expression of cytokines and adhesion molecules. Mechanistically, GCs diffuse through the cell membrane, and bind to their inactive cytosolic receptors (GRs), which then undergo conformational modifications that allow for their nuclear translocation. In the nucleus, activated GRs modulate transcriptional events by directly associating with DNA elements, compatible with the GCs response elements (GRE) motif, and located in variable copy numbers and at variable distances from the TATA box, in the promoter region of GC-responsive genes. In addition, activated GRs also acted by antagonizing the activity of transcription factors, in particular nuclear factor-κB (NF-κB), by direct and indirect mechanisms. GCs induced gene transcription and protein synthesis of the NF-κB inhibitor, IκB. Activated GR also antagonized NF-κB activity through protein-protein interaction involving direct complexing with, and inhibition of, NF-κB binding to DNA (Simple Model), or association with NF-κB bound to the κB DNA site (Composite Model). In addition, and according to the Transmodulation Model, GRE-bound GR may interact with and inhibit the activity of κB-bound NF-κB via a mechanism involving cross-talk between the two transcription factors. Lastly, GR may compete with NF-κB for nuclear coactivators, including CREB binding protein and p300, thereby reducing and inhibiting transcriptional activation by NF-κB. It should be noted that, in exerting its effect, activated GR did not affect the correct assembly of the pre-initiation (DAB) complex, but acted rather more proximally in inhibiting the correct assembly of transcription factors in the promoter region, and thus transcriptional initiation.

show abstract

Section: Glucocorticoid Antiproliferative Effectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Negative regulation of nuclear factor-kappaB activation and function by glucocorticoids

Almawi¹,

Melemedjian²

2002

Journal of Molecular Endocrinology

216

126

View full text Add to dashboard Cite

show abstract

Decreased expression of interleukin-1α, interleukin-1β, and cell adhesion molecules in muscle tissue following corticosteroid treatment in patients with polymyositis and dermatomyositis

Lundberg

Kratz

Alexanderson

et al. 2000

Arthritis & Rheumatism

114

View full text Add to dashboard Cite

Objective. To study the effects of immunosuppres-sive therapy, in particular, corticosteroids, on morpho-logic signs of inflammation and expression of cytokines, adhesion molecules, and class I major histocompatibil-ity complex (MHC) antigen in muscle tissue from patients with polymyositis (PM) and dermatomyositis (DM) and to correlate the molecular changes with changes in muscle function. Methods. Seven patients with PM and 4 patients with DM underwent muscle biopsy before and after 3-6 months of therapy. Ten of the 11 patients were initially treated with prednisolone 30-60 mg/day. The phenotypes of infiltrating inflammatory cells and the expression of interleukin-1 (IL-1) and IL-1, adhesion molecules, and class I MHC antigen were studied by immunochemistry. Computerized image analysis was used for quantitation of staining. Muscle function was assessed with a muscle function index score. Results. Pronounced improvement of muscle function during the treatment period was noted in 8 of the 11 patients. The changes in muscle function coincided with an almost complete disappearance of inflam-matory cells, including CD3 T cells, in the patients with clinical improvement. These patients also exhibited decreased expression of IL-1, IL-1, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), leukocyte function-associated antigen 1, and very late activation antigen 4. Of note, there was persistent expression of IL-1, ICAM-1, and VCAM-1 in capillaries and of class I MHC antigens on muscle fibers in several of the patients who, after corticosteroid treatment, still had muscle weakness despite the disappearance of inflammatory infiltrates. Conclusion. Changes in the muscle expression of key molecules in the inflammatory process, such as IL-1 and IL-1, ICAM-1 and class I MHC antigens, showed a consistent but not complete concordance with changes in and status of muscle function in patients with myositis who received the current standard treatment for the disease. These data indicate that it is possible to further evaluate various therapies for myo-sitis using molecular analysis of muscle biopsy specimens obtained on repeated occasions. In addition, the data demonstrate a dissociation between muscle function and degree of inflammatory infiltration in the affected muscles and suggest that the functional defects are more related to the expression of molecules such as IL-1 in muscle capillaries than to the mere presence of inflammatory cells in the affected muscles.

show abstract

Materials in particulate form for tissue engineering. 2. Applications in bone

Silva

Coutinho

Ducheyne

et al. 2007

J Tissue Eng Regen Med

100

View full text Add to dashboard Cite

Materials in particulate form have been the subjects of intensive research in view of their use as drug delivery systems. While within this application there are still issues to be addressed, these systems are now being regarded as having a great potential for tissue engineering applications. Bone repair is a very demanding task, due to the specific characteristics of skeletal tissues, and the design of scaffolds for bone tissue engineering presents several difficulties. Materials in particulate form are now seen as a means of achieving higher control over parameters such as porosity, pore size, surface area and the mechanical properties of the scaffold. These materials also have the potential to incorporate biologically active molecules for release and to serve as carriers for cells. It is believed that the combination of these features would create a more efficient approach towards regeneration. This review focuses on the application of materials in particulate form for bone tissue engineering. A brief overview of bone biology and the healing process is also provided in order to place the application in its broader context. An original compilation of molecules with a documented role in bone tissue biology is listed, as they have the potential to be used in bone tissue engineering strategies. To sum up this review, examples of works addressing the above aspects are presented. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE R E V I E W A R T I C L E AbstractMaterials in particulate form have been the subjects of intensive research in view of their use as drug delivery systems. While within this application there are still issues to be addressed, these systems are now being regarded as having a great potential for tissue engineering applications. Bone repair is a very demanding task, due to the specific characteristics of skeletal tissues, and the design of scaffolds for bone tissue engineering presents several difficulties. Materials in particulate form are now seen as a means of achieving higher control over parameters such as porosity, pore size, surface area and the mechanical properties of the scaffold. These materials also have the potential to incorporate biologically active molecules for release and to serve as carriers for cells. It is believed that the combination of these features would create a more efficient approach towards regeneration. This review focuses on the application of materials in particulate form for bone tissue engineering. A brief overview of bone biology and the healing process is also provided in order to place the application in its broader context. An original compilation of molecules with a documented role in bone tissue biology is listed, as they have the potential to be used in bone tissue engineering strategies. To sum up this review, examples of works addressing the above aspects are presented.

show abstract

Multiplicity of glucocorticoid action in inhibiting allograft rejection

Cited by 32 publications

References 175 publications

Negative regulation of nuclear factor-kappaB activation and function by glucocorticoids

Negative regulation of nuclear factor-kappaB activation and function by glucocorticoids

Decreased expression of interleukin-1α, interleukin-1β, and cell adhesion molecules in muscle tissue following corticosteroid treatment in patients with polymyositis and dermatomyositis

Materials in particulate form for tissue engineering. 2. Applications in bone

Contact Info

Product

Resources

About