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Expression of Th1 and Th2 Cytokine and Associated Transcription Factors in Peripheral Blood Mononuclear Cells and Correlation with Disease Severity.

ABSTRACT: BACKGROUND:Psoriasis is a T cell-mediated autoimmune disease in patients with elevated levels of proinflammatory cytokines belonging mainly to the Th1 pathway. We investigated whether treatment of psoriasis patients with methotrexate (MTX), along with micronutrients, modulated mRNA expression of Th1 and Th2 components and whether expression of these components correlated with psoriasis severity. METHODS:Thirty plaque-type psoriasis patients with Psoriasis Area and Severity Index (PASI) scores greater than 10 were recruited; these were 15 non-micronutrients taking- (NMT) patients treated with MTX daily (0.2-0.3 mg/kg/week), and 15 micronutrients taking- (MT) patients treated with MTX plus a micronutrient supplement daily, for 12 weeks. Blood samples were collected immediately before treatment (baseline) and after 12 weeks of treatment. Taqman quantitative real-time polymerase chain reaction (qPCR) was applied to analyze the expression of the Th1 components T-bet, interleukin-12 (IL-12), and interferon-gamma (IFN-?), and the Th2 components GATA-3 and interleukin-4 (IL-4). Disease severity was measured using the PASI scoring system. RESULTS:Significant clinical improvement in the MT group coincided with significant down-regulation of Th1 and up-regulation of Th2 markers (P<0.05). With respect to the PASI-75, (defined as a 75% or greater reduction in the PASI score) cut-off point, expression of IFN-? in the MT group with PASI scores above 75 was significantly less than that of patients in the NMT group (P=0.05). Also, GATA3 and IL-4 mRNA expression in the MT group with PASI scores greater than above 75 was significantly greater than that of patients in the NMT group (P=0.05 and 0.04, respectively). CONCLUSION:Based on significant attenuation of the PASI score, which correlated with upregulation of Th2 pathway markers in the MT group, we recommend administration of micronutrients combined with MTX for psoriasis patients. Our results contribute to a better understanding of methotrexate immunepathogenesis mechanisms and their correlations to clinical responses in psoriasis.

SUBMITTER: Yousefzadeh H

PROVIDER: S-EPMC5643454 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Expression of Th1 and Th2 Cytokine and Associated Transcription Factors in Peripheral Blood Mononuclear Cells and Correlation with Disease Severity.

Yousefzadeh Hadis H Jabbari Azad Farahzad F Rastin Maryam M Banihashemi Mahnaz M Mahmoudi Mahmoud M

Reports of biochemistry & molecular biology 20171001 1

<h4>Background</h4>Psoriasis is a T cell-mediated autoimmune disease in patients with elevated levels of proinflammatory cytokines belonging mainly to the Th1 pathway. We investigated whether treatment of psoriasis patients with methotrexate (MTX), along with micronutrients, modulated mRNA expression of Th1 and Th2 components and whether expression of these components correlated with psoriasis severity.<h4>Methods</h4>Thirty plaque-type psoriasis patients with Psoriasis Area and Severity Index ( ...[more]

PMID: 29090236

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Project description:Background:Silver nanoparticles (AgNPs) have been widely used in many commercial products due to their excellent antibacterial ability. The AgNPs are released into the environment, gradually accumulate in the ocean, and may affect animals at high trophic levels, such as cetaceans and humans, via the food chain. Hence, the negative health impacts caused by AgNPs in cetaceans are of concern. Cytokines play a major role in the modulation of immune system and can be classified into two types: Th1 and Th2. Th1/Th2 balance can be evaluated by the ratios of their polarizing cytokines (i.e., interferon [IFN]-?/Interleukin [IL]-4), and animals with imbalanced Th1/Th2 response may become more susceptible to certain kinds of infection. Therefore, the present study evaluated the in vitro cytokine responses of cetacean peripheral blood mononuclear cells (cPBMCs) to 20 nm citrate-AgNPs (C-AgNP20) by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Methods:Blood samples were collected from six captive common bottlenose dolphins (Tursiops truncatus). The cPBMCs were isolated and utilized for evaluating the in vitro cytokine responses. The cytokines evaluated included IL-2, IL-4, IL-10, IL-12, interferon (IFN)-?, and tumor necrosis factor (TNF)-?. The geometric means of two housekeeping genes (HKGs), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and ?2-microglobulin (B2M), of each sample were determined and used to normalize the mRNA expression levels of target genes. Results:The ratio of late apoptotic/necrotic cells of cPBMCs significantly increased with or without concanavalin A (ConA) stimulation after 24 h of 10 µg/ml C-AgNP20 treatment. At 4 h of culture, the mRNA expression level of IL-10 was significantly decreased with 1 µg/ml C-AgNP20 treatment. At 24 h of culture with 1 µg/ml C-AgNP20, the mRNA expression levels of all cytokines were significantly decreased, with the exceptions of IL-4 and IL-10. The IFN-?/IL-4 ratio was significantly decreased at 24 h of culture with 1 µg/ml C-AgNP20 treatment, and the IL-12/IL-4 ratio was significantly decreased at 4 or 24 h of culture with 0.1 or 1 µg/ml C-AgNP20 treatment, respectively. Furthermore, the mRNA expression level of TNF-? was significantly decreased by 1 µg/ml C-AgNP20 after 24 h of culture. Discussion:The present study demonstrated that the sublethal dose of C-AgNP20 (?1 µg/ml) had an inhibitory effect on the cytokine mRNA expression levels of cPBMCs with the evidence of Th2 cytokine bias and significantly decreased the mRNA expression level of TNF-?. Th2 cytokine bias is associated with enhanced immunity against parasites but decreased immunity to intracellular microorganisms. TNF-? is a contributing factor for the inflammatory response against the infection of intracellular pathogens. In summary, our data indicate that C-AgNP20 suppresses the cellular immune response and thereby increases the susceptibility of cetaceans to infection by intracellular microorganisms.

Project description:Peripheral blood mononuclear cells (PBMCs) discriminate microbial pathogens and induce T-cell responses of appropriate effector phenotype accordingly. Toll-like receptors (TLRs), in part, mediate this microbial recognition and differentiation while the development of T-cell effector functions critically depends on the release of Th1- or Th2- type cytokines. In the present study, buffalo PBMCs were stimulated under in vitro culture conditions by Bacillus subtilis cell wall petidoglycan, a TLR2 ligand, in a dose-and time- dependent manner. The expression of TLR2 as well as the subsequent differential induction of the Th1 and Th2 type cytokines was measured. Stimulation was analyzed across five doses of peptidoglycan (10 ?/ml, 20 ?g/ml, 30 ?g/ml, 40 ?g/ml and 50 ?g/ml) for 3 h, 12 h, 24 h and 36 h incubation periods. We observed the induction of TLR2 expression in a dose- and time-dependent manner and the peptidoglycan induced tolerance beyond 30 ?g/ml dose at all incubation periods. The correlation between peptidoglycan stimulation and TLR2 induction was found positive at all doses and for all incubation periods. Increased production of all the cytokines was observed at low doses for 3 h incubation, but the expression of IL-4 was relatively higher than IL-12 at the higher antigen doses, indicating tailoring towards Th2 response. At 12 h incubation, there was a pronounced decrease in IL-4 and IL-10 expression relative to IL-12 in a dose- dependent manner, indicating skewing to Th1 polarization. The expression of IL-12 was highest for all doses across all the incubation intervals at 24 h incubation, indicating Th1 polarization. The relative expression of TNF-? and IFN-? was also higher while that of IL-4 and IL-10 showed a decrease. For 36 h incubation, at low doses, relative increase in the expression of IL-4 and IL-10 was observed which decreased at higher doses, as did the expression of all other cytokines. The exhaustion of cytokine production at 36 h indicated that PBMCs became refractory to further stimulation. It can be concluded from this study that the cytokine response to sPGN initially was of Th2 type which skews, more pronouncedly, to Th1 type with time till the cells become refractory to further stimulation.

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Expression of Th1 and Th2 Cytokine and Associated Transcription Factors in Peripheral Blood Mononuclear Cells and Correlation with Disease Severity.

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Expression of Th1 and Th2 Cytokine and Associated Transcription Factors in Peripheral Blood Mononuclear Cells and Correlation with Disease Severity.

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