Dataset Information

Possible role of BMP-4 in the hyper-pigmentation of psoriatic plaques after anti-TNF-? treatment.

ABSTRACT: Psoriasis over-expresses several inflammatory mediators, which impacts the activity of melanocytes. Tyrosinase (Tyr) and microphthalmia-associated transcription factor (MITF) are the primary regulators of melanogenesis. Furthermore, bone morphogenetic proteins (BMPs) modulate various pathobiologic processes including inflammation, melanogenesis and melanomagenesis. To determine the association between psoriasis and melanogenesis, psoriatic lesional skin was screened through gene expression, immunohistochemistry, immunogold staining and melanin content assays. The present study detected a decreased expression of Tyr, MITF and BMP-4 in psoriatic lesional skin compared with healthy skin. Tyr, BMP-4 and melanin content were also evaluated in the psoriatic lesional skin of patients receiving adalimumab therapy, before and after 16 weeks of treatment. TNF-? blockade modulated the Tyr, BMP-4 and melanin content of the patient skin lesions, which supported the hypothesis that hyper-pigmentation may occur in areas of psoriatic plaque after biological treatment. The present study confirmed the influence of the psoriatic pro-inflammatory network on melanogenesis, exerting an inhibitory effect mediated by TNF-?. Furthermore, the results regarding BMP-4 in the present study add another important element to the mechanism of psoriasis.

SUBMITTER: Di Costanzo L

PROVIDER: S-EPMC6781796 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Possible role of BMP-4 in the hyper-pigmentation of psoriatic plaques after anti-TNF-α treatment.

Di Costanzo Luisa L Scala Emanuele E Caiazzo Giuseppina G Lembo Serena S Marino Rita R Megna Matteo M Patrì Angela A Di Caprio Roberta R Balato Anna A

Experimental and therapeutic medicine 20190917 5

Psoriasis over-expresses several inflammatory mediators, which impacts the activity of melanocytes. Tyrosinase (Tyr) and microphthalmia-associated transcription factor (MITF) are the primary regulators of melanogenesis. Furthermore, bone morphogenetic proteins (BMPs) modulate various pathobiologic processes including inflammation, melanogenesis and melanomagenesis. To determine the association between psoriasis and melanogenesis, psoriatic lesional skin was screened through gene expression, immu ...[more]

PMID: 31611943

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Project description:In 15 patients with rheumatoid arthritis the baseline expression (t=0) of type I IFN-regulated genes was determined in peripheral blood cells (PAXgene) using cDNA-microarrays and compared to levels one month after (t=1) anti-TNF treatment (infliximab). Therefore, we used 43K cDNA microarrays from the Stanford Functional Genomics Facility (http://microarray.org/sfgf/) printed on aminosilane-coated slides containing ~20.000 unique genes. Only one batch of arrays was used for all experiments. First DNA spots were UV-cross linked to the slide using 150-300 mJoules. Sample preparation and microarray hybridization were performed as described previously (1,2). Data storage and filtering was performed using the Stanford Microarray Database (http://genome-www5.stanford.edu//) as described previously. 1. van der Pouw Kraan TC, Wijbrandts CA, van Baarsen LG, Voskuyl AE, Rustenburg F, Baggen JM et al.: Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: assignment of a type I interferon signature in a subpopulation of patients. Ann Rheum Dis 2007, 66: 1008-1014. 2. van der Pouw Kraan TC, van Baarsen LG, Rustenburg F, Baltus B, Fero M, Verweij CL: Gene expression profiling in rheumatology. Methods Mol Med 2007, 136: 305-327. Abbreviations: - Bnrs are the different patients analyzed - PAX or Paxgene indicates the total RNA was isolated from peripheral blood obtained in PAXgene tubes - CRS: common reference sample: We made a common reference that consisted of a mixture of mRNAs isolated from 11 different cell lines (Perou CM, Jeffrey SS, van de RM et al. Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proc Natl Acad Sci U S A. 1999; 96:9212-9217) supplemented with RNA from rheumatoid synovial tissue, fibroblasts, and activated peripheral blood mononuclear cells (PBMCs). - PMT: photomultiplier tube: the sensitivity/intensity of the scanner can be adjusted to prevent spot saturation. Compound Based Treatment: anti-TNF (infliximab) reference_design

Project description:TNF weakly inducer of apoptosis (TWEAK) is member of the TNF ligand superfamily. Various data support that TWEAK produced by synovial macrophages may contribute to synovitis observed in psoriatic arthritis (PsoA). In PsoA, anti-TNF therapy has been successful in agreement with the key role of TNF in the pathogenesis and the generation by PsoA patients of anti-TNF autoantibodies referred as "beneficial autoimmunity to pro-inflammatory mediators". However, the role of TNF-alpha in the regulation of TWEAK modulation of inflammation during PsoA remains unknown.We have studied level course during anti-TNF therapy of serum soluble TWEAK. In the same cohort, we have investigated the generation of TWEAK-binding autoantibodies by PsoA patients before and after anti-TNF therapy.Patients with PsoA had significantly higher serum levels of TWEAK compared with controls [respective means (±SEM) were 645 pg/ml (64) and 467 pg/ml (23); (p = 0.006)] but serum soluble TWEAK levels were not correlated with BASDAI (Spearman's coefficients <0.003, p > 0.05). Our study showed that soluble TWEAK levels were not modulated by etanercept therapy [respective Means (±SEM) were 605 (95) (week 12) and 744 (97) (week 24) pg/ml; (p > 0.23)]. Anti-TWEAK autoantibodies were detected in 9/13 (69.2 %) PsoA patients at inclusion and only in 3/57 (5.3 %) healthy blood donors (p < 0.0001). These circulating antibodies were persistent in PsoA patients and detected at similar levels during etanercept therapy. Moreover we showed that they had a down regulating effect on CCL-2 secretion by endothelial cells stimulated by rh TWEAK in vitro.Our study revealed that during psoriatic arthritis (1) serum TWEAK was up regulated and (2) TWEAK-binding autoantibodies are generated. Both parameters were not influenced by anti-TNF therapy and persisted at high levels during anti-TNF therapy. For the first time we described here TWEAK-binding IgG autoantibodies with a down regulating effect on CCL-2 secretion by endothelial cells stimulated by rh TWEAK in vitro. Finally, our results suggest that TWEAK may be involved in PsoA pathogeny. Trial registration This clinical trial was approved by the local Ethics Committee "Comité de Protection des Personnes Sud-Méditerranée V" with the registration number: 2011-002954-29, and French health minister registration number AFSSAPS A110784-42 obtained the 08/22/2011. This clinical trial is registered in Clinical trial.gov under the number: NCT02164214.

Dataset Information

Possible role of BMP-4 in the hyper-pigmentation of psoriatic plaques after anti-TNF-? treatment.

Publications

Possible role of BMP-4 in the hyper-pigmentation of psoriatic plaques after anti-TNF-α treatment.

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