Biological therapies in the systemic management of psoriasis: International Consensus Conference

Sterry, Wolfram; Barker, J N W N; Boehncke, W. H.; Bos, Jan D.; Chimenti, Sergio; Christophers, Enno; Brassinne, M de la; Ferrándiz, Carlos; Griffiths, Christopher E.M.; Katsambas, Andreas; Kragballe, Knud; Lynde, Charles; Menter, Alan; Ortonne, Jean‐Paul; Papp, Kim; Prinz, JC; Rzany, Berthold; Rönnevig, J.R.; Saurat, J.‐H.; Ståhle, Mona; Stengel, Fernando; Kerkhof, P.C.M. van de; Voorhees, John J.

doi:10.1111/j.1365-2133.2004.06070.x

Cited by 176 publications

(153 citation statements)

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“…Though there is increasing evidence that T-cell dysregulation is involved in the development and maintenance ofpsoriasis (30)(31)(32), for which AEB071 has been proposed as a promising therapeutic agent (14,18), the role of neutrophils in its pathogenesis has also been described: phagocytes are required for the development of psoriatic plaques and are an important pathogenic factor potentiating T cellassociated inflammation (33,34). In addition, the potential tissue damaging effect of neutrophils in non-infectious inflammatory disorders is recognized and was recently reviewed (26).…”

Section: Cytokine Productionmentioning

confidence: 99%

The Protein Kinase C Inhibitor Aeb071 (Sotrastaurin) Modulates Migration and Superoxide Anion Production by Human Neutrophils In Vitro

Capsoni

Ongari

Reali

et al. 2012

Int J Immunopathol Pharmacol

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We examined the effect ofthe protein kinase C-selective inhibitorAEB071 (sotrastaurin) on neutrophil functions in vitro. Pre-incubation with AEB071 at concentrations similar to those reached during in vivo therapy significantly reduced cell capacity to migrate toward three different chemo-attractants and to produce superoxide anions (02-) in response to phorbol myristate acetate (PMA) or to N-formylmethionyl-Ieucyl-phenylalanine (tMLP). AEB071 also significantly inhibited the 02-overproduction induced by tMLP in neutrophils primed with tumor necrosis factor alpha (TNF-a) or granulocyte/ macrophage-colony stimulating factor (GM-CSF). This inhibition was not linked to tMLP-receptor down-regulation since the drug had no effect on either tMLP-receptors or tMLP-induced CDllb membrane expression. When the activity of AEB071 was compared to that of the conventional protein kinase C (PKC) inhibitor Go6850 (which, like sotrastaurin, inhibits classical and novel PKC isoforms), G06976 (an inhibitor of a and p PKC isoforms) and rottlerin (a prevailing () PKC isoform inhibitor), AEB071 at an equimolar concentration of 3 JIM (close to the maximum drug concentration reached in patients treated with AEB071) caused significantly more inhibition on both chemotactic response and superoxide production. These in vitro findings suggest that neutrophils may offer a cellular target for AEB071 activity in vivo.Protein kinase C (PKC) is a family of multifunctional serine/threonine kinases which have regulatory roles in all aspects of eukaryotic cell function (1, 2). This family comprises at least ten isoforms divided into three groups on the basis of molecular structure and biochemical properties: classical PKC isoforms (a,~I,~II and y), novel PKC (8, E, eand TJ) and atypical PKC (~and t / A).PKC are expressed in various cell types and regulate many different cellular processes. Only recently in vitro studies and particularly in vivo studies of PKC isoform-selective knockout mice have clarified the unique function of each isotype in the immune system. Specifically, PKC a and PKC efunction in T-cell signaling and survival (3-5), PKC~and PKC 8 in B-cell signaling and survival (6-8) and PKC E in macrophage and dendritic cell activation (9).In animal models PKC 8 is involved in induction oftolerance (8) and PKC~in B-cell antigen receptor function (7). Thus, PKC isoforms in T and B cells have been proposed as attractive therapeutic targets for transplantation, inflammatory and autoimmune

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Section: Cytokine Productionmentioning

confidence: 99%

The Protein Kinase C Inhibitor Aeb071 (Sotrastaurin) Modulates Migration and Superoxide Anion Production by Human Neutrophils In Vitro

Capsoni

Ongari

Reali

et al. 2012

Int J Immunopathol Pharmacol

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show abstract

“…An understanding of immune mechanisms contributing to disease expression has led to the development of selective, and probably safer, long-term therapies in the form of biologics. 19 At the same time, awareness that patients need to be treated as individuals with differing psychological needs has ushered in the biopsychosocial approach to management.…”

Section: Discussionmentioning

confidence: 99%

“…17 [12][13][14][15]19 viously been shown to be successful in patients with cancer and rheumatic diseases. Similar results were found for psoriasis in a study by Fortune et al 18 in which 93 patients with psoriasis were allocated to receive either standard psoriasis treatment alone or to enter a Psoriasis Symptom Management Programme (PSMP) which included cognitive behavioural therapy and relaxation techniques as an adjunct to standard therapy.…”

Section: Cognitive Behavioural Therapymentioning

confidence: 99%

Modern management of psoriasis

2005

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“…Unlike in other inflammatory diseases, such as rheumatoid arthritis, the risk of obesity is strongly associated with disease severity (Sterry W et al, 2004).…”

Section: Obesity and Psoriasismentioning

confidence: 99%