Heme oxygenase and iron status in exosomes of psoriasis patients

Abstract

Psoriasis is an autoimmune skin disease characterized by hyperproliferation of keratinocytes due to interplay between keratinocytes and immune cells. Iron status plays an important role in modifying the function of the immune system. Heme oxygenase (HO), heme-degrading enzyme, plays important role in protective response to oxidative cellular stress. We aimed in this study to map the iron status and HO levels and declare the role HO enzyme in iron homeostasis and immune-modulation in psoriasis. Fifty-one patients with psoriasis and 50 age- and sex-matched healthy controls were enrolled in this study. 5 mL blood sample was withdrawn from each subject. Hepcidin, iron soluble transferring receptor (sTfR), and total iron binding capacity (TIBC) were estimated using ELISA technique and, HO-1 gene level was detected using RT-PCR (reverse transcription-polymerase chain reaction). Iron levels, TIBC, and hepcidin were significantly lower in cases compared to controls. On the contrary, sTfR and HO-1 were significantly over-expressed in cases compared to controls (p < 0.05 in all). HO-1 expression negatively correlated with PASI score and disease extent (%) (r = - 0.614-, p = 0.001; r = - 0.807-, p = 0.001 respectively). There were no significant associations between HO-1 expression and iron, TIBC, hepcidin, sTfR levels (p > 0.05 in all). Iron supplements for the patients with psoriasis are important to maintain haematopoiesis. The induction of HO-1 might have be a promising approach for the treatment of psoriasis through antioxidant ability, immunomodulatory role as well as its role in heme synthesis.

Effect of Iron Supplementation on the Outcome of Non-Progressive Pulmonary Mycobacterium tuberculosis Infection

“…HAMP binds to FPN and induces its internationalization and subsequent degradation, thereby reducing Fe release from macrophages and enterocytes [28]. FTH1 is a subunit of ferritin, an Fe-storage protein [29], and HMOX is an enzyme involved in heme catabolism, both of which are regulated by host Fe status [30]. NRF2, a regulator of the antioxidant response, also regulates FTH1 and FPN to maintain cellular Fe homeostasis [31].…”

Characterization and heme oxygenase‐1 content of extracellular vesicles in human biofluids

“…This upper band may represent either bound NADPH:cytochrome P450 reductase (Linnenbaum, Busker, Kraehling, & Behrends, 2012; Sato, Kato, & Arawaka, 2013), a key electron donor in the HO‐1‐catalyzed heme degradation pathway, or a multimeric form of HO‐1 (Hwang et al., 2009; Linnenbaum et al., 2012). Others have shown the presence of HO‐1 mRNA in EVs (El‐Rifaie et al., 2018), and mass spectrometry analyses have identified HO‐1 in proteomic profiles of healthy human urinary EVs (Wang et al., 2012) as well as EVs released by various cancer cells (Kalra et al., 2012). In contradistinction to EV HO‐1, total extracellular HO‐1 has been studied extensively as a potential biomarker in various disease states.…”

“…The presence of HO‐1 messenger RNA (mRNA) or protein in EVs has been minimally described in the literature. El‐Rifaie and colleagues reported increased HO‐1 mRNA in exosomes isolated from peripheral blood mononuclear cells of psoriasis patients (El‐Rifaie, Sabry, Doss, Kamal, & Abd El Hassib, 2018). Furthermore, exosomes released from bovine granulosa cells challenged with hydrogen peroxide in vitro resulted in significant elevation of nuclear factor erythroid 2‐related factor 2 mRNA and downstream antioxidants (e.g., catalase, thioredoxin), though lower levels of HO‐1 mRNA were recorded (Saeed‐Zidane et al., 2017).…”

Clinical Significance of Heme Oxygenase 1 in Tumor Progression

“…More recently, the involvement of extracellular vesicles (EVs), such as exosomes and micro-vesicles, as potential sources of extracellular biomarkers has been considered [ 104 , 105 ]. In this context, HO-1 mRNA and protein have been detected in exosomes isolated from peripheral blood mononuclear cells (PMBC) of psoriasis patients [ 106 ]. Schipper and coworkers detected HO-1 protein in EVs from various human bio fluids [ 107 ].…”