Studies of the Effect of Cyclosporine in Psoriasis In Vivo: Combined Effects on Activated T Lymphocytes and Epidermal Regenerative Maturation

Gottlieb, Alice B.; Grossman, Rachel; Khandke, Lakshmi; Carter, D Martin; Sehgal, Pravinkumar B.; Fu, Shu Man; Granelli‐Piperno, Angela; Rivas, Miriam V.; Barazani, Lance; Krueger, James G.

doi:10.1111/1523-1747.ep12499782

Cited by 96 publications

(68 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…12 Cyclosporin A is an immunosuppressant drug active in psoriasis that also inhibits proinflammatory cytokine mRNA production in psoriatic lesions. 2,5 Mechanistically Cyclosporin A is distinct from rhIL-11 with inhibitory effects on T cell activation particularly through blockade of the calcineurin/NFAT and p38/JNK signaling pathways. 13,14 Comparisons of gene expression levels between uninvolved and lesional skin following treatment with rhIL-11 or Cyclosporin A cover a diverse spectrum of pathways of therapeutic intervention for inflammatory and autoimmune diseases.…”

Section: Pharmacological Treatment Of Patients Identifies Pharmacogenmentioning

confidence: 99%

“…Response rates of these patients were typical of those previously reported. 2,5 Sixty per cent of rhIL-11-treated and 90% of Cyclosporin Atreated patients were considered to have responded to therapy as defined by changes in several clinical and histopathological criteria. 5 To identify genes whose expression patterns change over the course of drug treatment, comparisons in expression profiles of lesional skin were made between responding and non-responding patients prior to drug treatment and at weeks 1, 4, 8 and 12 following initiation of therapy.…”

Section: Pharmacological Treatment Of Patients Identifies Pharmacogenmentioning

confidence: 99%

“…2 The grading system used to measure local clinical disease activity was the Psoriasis Severity Index (PSI). The PSI index grades individual psoriasis lesions for scale, erythema, and induration on a 0-6 point scale for each parameter (0, absent; 1, trace; 2, mild; 3, mild to moderate; 4, moderate; 5, moderate to severe; and 6, severe).…”

Section: Study Design and Psoriasis Patient Entry Criteriamentioning

confidence: 99%

“…1 The therapeutic benefit of immunosuppressive drugs, eg, Cyclosporin A, FK506, anti-CD4 antibody and IL-2 diphtheria toxin conjugate supports the hypothesis that activated immune cells, particularly T cells are pathogenic effectors of psoriasis. [2][3][4] More recently, treatment of psoriasis patients with the immunomodulatory drug, recombinant human interleukin-11, resulted in a downregulation of type 1 cytokines suggesting a role for Th1-specific cells in disease progression. 5 As a result of these studies, there is broad interest among researchers in using psoriasis as a 'model' inflammatory disease mediated by Type 1 T-cells and many new anti-inflammatory or immune-modulating drugs are now tested for the first time in humans in this disease.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling

Oestreicher¹,

et al. 2001

View full text Add to dashboard Cite

Psoriasis is recognized as the most common T cell-mediated inflammatory disease in humans. Genetic linkage to as many as six distinct disease loci has been established but the molecular etiology and genetics remain unknown. To begin to identify psoriasis disease-related genes and construct in vivo pathways of the inflammatory process, a genome-wide expression screen of multiple psoriasis patients was undertaken. A comprehensive list of 159 genes that define psoriasis in molecular terms was generated; numerous genes in this set mapped to six different disease-associated loci. To further interpret the functional role of this gene set in the disease process, a longitudinal pharmacogenomic study was initiated to understand how expression levels of these transcripts are altered following patient treatment with therapeutic agents that antagonize calcineurin or NF-B pathways. Transcript levels for a subset of these 159 genes changed significantly in those patients who responded to therapy and many of the changes preceded clinical improvement. The disease-related gene map provides new insights into the pathogenesis of psoriasis, wound healing and cellular-immune reactions occurring in human skin as well as other T cell-mediated autoimmune diseases. In addition, it provides a set of candidate genes that may serve as novel therapeutic intervention points as well as surrogate and predictive markers of treatment outcome.

show abstract

Section: Pharmacological Treatment Of Patients Identifies Pharmacogenmentioning

confidence: 99%

Section: Pharmacological Treatment Of Patients Identifies Pharmacogenmentioning

confidence: 99%

Section: Study Design and Psoriasis Patient Entry Criteriamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling

Oestreicher¹,

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Multiple ErbB ligands as well as ErbB-1 are upregulated during the early phases of wound healing and in psoriasis, a disease which has been likened to dysregulated wound healing (Cook et al, 1991;Elder, 1994;Gottlieb et al, 1992;Nanney et al, 1986;Stoll et al, 1997;Stoscheck et al, 1992;Wenczak et al, 1992). Bcl-X L has been shown to be strongly upregulated in psoriatic skin, whereas bcl-2 was essentially undetectable (Wrone-Smith et al, 1995).…”

mentioning

confidence: 99%

EGF receptor signaling inhibits keratinocyte apoptosis: evidence for mediation by Bcl-XL

et al. 1998

View full text Add to dashboard Cite

Signaling through the epidermal growth factor receptor (EGFR) has been primarily implicated in the growth of epithelial cells including keratinocytes. However, the mechanism by which EGFR stimulation promotes keratinocyte cell growth is poorly understood. Here we report that human keratinocytes undergo apoptosis when incubated with the blocking EGFR monoclonal antibody 225 IgG, or PD153035, a highly speci®c EGFR tyrosine kinase inhibitor. Endogenous mRNA and protein levels of Bcl-X L , a member the Bcl-2 family which suppresses apoptosis, were speci®cally inhibited by EGFR blockade. Furthermore, stimulation of EGFR signaling through two natural ligands, transforming growth factor (TGF)-a and epidermal growth factor (EGF), increased the expression of Bcl-X L in quiescent keratinocytes and HaCaT cells. Finally, ectopic expression of Bcl-X L in HaCaT cells increased survival after EGFR blockade when compared to untransfected cells or HaCaT keratinocytes transfected with empty vector. These results suggest that the anti-apoptotic protein Bcl-X L plays an important role in the maintenance of keratinocyte survival in response to EGFR signaling.

show abstract

Clinical Clearing of Psoriasis by 6-Thioguanine Correlates With Cutaneous T-Cell Depletion via Apoptosis

Murphy¹,

Coven²,

Burack³

et al. 1999

Arch Dermatol

View full text Add to dashboard Cite

Studies of the Effect of Cyclosporine in Psoriasis In Vivo: Combined Effects on Activated T Lymphocytes and Epidermal Regenerative Maturation

Cited by 96 publications

References 45 publications

Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling

Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling

EGF receptor signaling inhibits keratinocyte apoptosis: evidence for mediation by Bcl-XL

Clinical Clearing of Psoriasis by 6-Thioguanine Correlates With Cutaneous T-Cell Depletion via Apoptosis

Contact Info

Product

Resources

About