Potential Role of Cytochrome c and Tryptase in Psoriasis and Psoriatic Arthritis Pathogenesis: Focus on Resistance to Apoptosis and Oxidative Stress

Abstract

Psoriasis (PsO) is an autoimmune disease characterized by keratinocyte proliferation, chronic inflammation and mast cell activation. Up to 42% of patients with PsO may present psoriatic arthritis (PsA). PsO and PsA share common pathophysiological mechanisms: keratinocytes and fibroblast-like synoviocytes are resistant to apoptosis: this is one of the mechanism facilitating their hyperplasic growth, and at joint level, the destruction of articular cartilage, and bone erosion and/or proliferation. Several clinical studies regarding diseases characterized by impairment of cell death, either due to apoptosis or necrosis, reported cytochrome c release from the mitochondria into the extracellular space and finally into the circulation. The presence of elevated cytochrome c levels in serum has been demonstrated in diseases as inflammatory arthritis, myocardial infarction and stroke, and liver diseases. Cytochrome c is a signaling molecule essential for apoptotic cell death released from mitochondria to the cytosol allowing the interaction with protease, as the apoptosis protease activation factor, which lead to the activation of factor-1 and procaspase 9. It has been demonstrated that this efflux from the mitochondria is crucial to start the intracellular signaling responsible for apoptosis, then to the activation of the inflammatory process. Another inflammatory marker, the tryptase, a trypsin-like serine protease produced by mast cells, is released during inflammation, leading to the activation of several immune cells through proteinase-activated receptor-2. In this review, we aimed at discussing the role played by cytochrome c and tryptase in PsO and PsA pathogenesis. To this purpose, we searched pathogenetic mechanisms in PUBMED database and review on oxidative stress, cytochrome c and tryptase and their potential role during inflammation in PsO and PsA. To this regard, the cytochrome c release into the extracellular space and tryptase may have a role in skin and joint inflammation.

A Multimodal Eye Assessment in Psoriatic Arthritis Patients sine-Psoriasis: Evidence for a Potential Association with Systemic Inflammation

“…These findings are consistent with the idea of multiorgan inflammatory involvement in PsA disease sine-PsO [8,31] as demonstrated in other chronic inflammatory disorders, such as PsO [8][9][10][11][12][13], diabetes mellitus [32,33], and thyreopathies [34]. In this context, the presence of dry eye might reflect the inflammatory status being an indicator of the systemic involvement in PsA [35]. The management of dysfunctional tear The mean thickness of the posterior pole from PsA patients was similar to those from healthy eyes at the hemi-superior and hemi-inferior fields and in the total scans (Table 1).…”

S-adenosylmethionine Decarboxylase 1 Participates in PM2.5 Exposure Induced Neuronal Apoptosis via Mitochondria-Mediated Pathway

“…Once activated, mitochondrial intermembrane space proteins, notably cytochrome C, are released into the cytosol whereupon they activate caspases. Executioner caspase, such as caspase 3, effectively kills the cell within minutes by cleavage of hundreds of different substrates in parallel [38][39][40]. By our results, the expression levels of mitochondrial function closely related protein Bax/Bcl-2, cytochrome C, cleaved caspase-9 and cleaved caspase-3 were up-regulated by PM 2.5 treatment, which could be recovered by spermidine pretreatment (Fig.…”

Koebner phenomenon leading to the formation of new psoriatic lesions: evidences and mechanisms

“…There have been a large number of studies documenting the key role of tryptase in the pathogenesis of psoriasis [66][67][68]. Tryptase is a trypsin-like serine protease, which is released by the mast cells during skin inflammatory reactions [69].…”