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Expression of Th1 and Th2 Cytokine and Associated Transcription Factors in Peripheral Blood Mononuclear Cells and Correlation with Disease Severity
Haadis Yousefzadeh, Farahzad Jabbari Azad, Maryam Rastin, Mahnaz Banihashemi, Mahmoud Mahmoudi,
Volume 6, Issue 1 (10-2017)
Abstract

Background: Psoriasis is a T cell-mediated autoimmune disease with elevated level of pro-inflammatory cytokines belonging mainly to Th1 pathway. We investigated whether treatment with micronutrients along with methotrexate (MTX) is able to modulate mRNA expression of Th1 and Th2 patterns and its correlation with disease severity.

Methods: Thirty plaque type psoriasis patients with Psoriasis Area and Severity Index (PASI) higher than 10 recruited; 15 non- micronutrients taker (NMT) patients, treated by MTX daily (0.2-0.3 mg/kg/week) and 15 micronutrients taker (MT) patients treated by MTX plus micronutrient supplement daily for 12 weeks. Blood samples collected at baseline and after 12 weeks. Taqman quantitative real-time polymerase chain reaction was applied to analyses the expression of Th1 (T-bet, IL-12, IFN- γ) and Th2 (GATA-3, IL-4) pathway. Disease severity measured under PASI scoring system.

Results: Significant clinical improvement in MT group was accordance with significant down-regulation of Th1 and up-regulation of Th2 studied markers (P<0.05). Respect to PASI-75 cut-point, expression of IFN-γ in MT group with upper PASI-75 was significantly lower than in related patients in NMT group (P=0.05). Also mRNA expressions of GATA3 and IL-4 in MT group with upper PASI-75 were significantly higher than patients in NMT group respectively (P=0.05, P=0.04)

Conclusion: According to significant attenuating of PASI score correlated with upregulation of Th2 pathway in favor of MT group, consumption of micronutrients in combination MTX in psoriasis patients are suggested. Our results contribute to a better understanding of methotrexate immune-pathogenesis mechanisms and its correlation to clinical response in psoriasis.  


Possible role of LncRNA MEG3-microRNA-21 and endoplasmic reticulum (ER) stress proteins in the Pathogenesis of Psoriasis Vulgaris
Zeinab Ahmad Nour, Yasmin Elwan, Yasser Nassar, Maha Fathy Elmasry, Laila Rashed, Sara Salama Ashour,
Volume 11, Issue 3 (11-2022)
Abstract
Background: Psoriasis is a chronic inflammatory immune mediated disease arising from interaction between genetic risk variants and the environment. Maternally expressed gene3 (MEG3) is a long noncoding RNA (lncRNA) known for gene transcription regulation and inhibiting proliferation. MEG3 competes with microRNA (miRNA-21) influencing cell proliferation and apoptosis balance. Endoplasmic reticulum (ER) stress proteins promote cell survival via unfolded protein response (UPR) influenced by MEG3. We aimed to detect the possible role of MEG3, miRNA-21 and ER stress proteins in pathogenesis of psoriasis vulgaris.
 
Methods: Human GRP78, ATF6, caspase3 tissue levels were assayed by Enzyme Linked Immunosorbent Assay (ELISA). Assessment of long non-coding MEG3 and miRNA 21 expressions was done by quantitative real time polymerase chain reaction (qRT-PCR).
 
Results: Expression of MEG3 was significantly downregulated, while miRNA-21 was remarkably upregulated, ER stress proteins GRP78, ATF6, and caspase 3 all showed low levels in homogenized psoriatic lesions when compared to normal skin. miRNA 21 and MEG3 were identified as possible diagnostic markers for psoriasis vulgaris.
 
Conclusions: MEG3 is barely expressed in psoriatic lesions while miRNA-21 expression is remarkably elevated but when correlated to each other there was unexpected positive correlation. MEG3 and miRNA-21 were identified as possible diagnostic markers for psoriasis. Undifferentiated psoriatic lesions have very weak UPR.

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