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Increased IL-4 mRNA expression and poly-aromatic hydrocarbon concentrations from children with asthma
Nasser M Al-Daghri1, Sherif Abd-Alrahman, Hossam Draz
1Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, PO Box, 2455, 11451 Riyadh, Saudi Arabia. aldaghri2011@gmail.com.
Insights
Pediatric asthma is linked to higher Interleukin-4 (IL-4) mRNA and serum levels, along with increased poly-aromatic hydrocarbon (PAH) exposure. PAH exposure in rats also elevated IL-4 mRNA, suggesting a role in asthma inflammation.
Area of Science:
- Immunology
- Environmental Health
- Pediatrics
Background:
- Asthma, a prevalent childhood illness, involves cytokine imbalances and environmental factors like poly-aromatic hydrocarbons (PAHs).
- T helper cell-derived cytokines, particularly Interleukin-4 (IL-4), are implicated in asthma pathogenesis.
- Poly-aromatic hydrocarbons (PAHs) are environmental pollutants recognized for their potential role in respiratory diseases.
Purpose of the Study:
- To compare mRNA expression of IL-4, interferon-gamma (IFN-γ), and ACSL3 in children with and without asthma.
- To correlate gene expression with serum levels of IL-4, IFN-γ, and PAHs.
- To investigate the effect of PAH exposure on IL-4, IFN-γ, and ACSL3 gene expression in a rat model.
Main Methods:
- Quantitative real-time PCR (qRTPCR) was used for gene expression analysis.
- Serum cytokine and PAH levels were measured using multiplex immunoassay kits and High-Performance Liquid Chromatography (HPLC).
- A rat model was utilized to study the in vivo effects of PAH exposure on gene expression.
Main Results:
- Children with asthma showed significantly higher IL-4 mRNA expression and serum IL-4 levels compared to controls.
- Elevated serum PAH concentrations were observed in asthmatic children, while IFN-γ levels were lower.
- In rats, exposure to a model PAH (benzopyrene) significantly increased IL-4 mRNA expression by 2.6-fold.
Conclusions:
- Elevated IL-4 mRNA and serum levels are associated with pediatric asthma.
- Increased PAH exposure is linked to asthma in children.
- PAH-induced IL-4 upregulation in animal models suggests a mechanism contributing to asthma-related inflammation.
Background:
Asthma is the most common chronic childhood disease. Imbalance of cytokines released from T helper cells and environmental factors, such as exposure to poly-aromatic hydrocarbon (PAH), play pivotal roles in the pathogenesis of asthma. The aim of this study was to compare the mRNA expression patterns of Interleukin (IL)-4, interferon (IFN)-γ and Acyl Co A long chain 3 (ACSL3) in peripheral blood leukocytes of children with and without asthma. To correlate the obtained mRNA data with serum IL-4, IFN-γ and PAH levels. Further, to determine the effect of in vivo exposure to PAH on mRNA expression of IL-4, IFN-γ and ACSL3 genes in a rat model.
Methods:
A total of 170 children below 16 years (85 pediatric asthma patients and 85 matched healthy controls) were randomly selected from the Riyadh Cohort, Saudi Arabia. Gene expression analysis was performed using qRTPCR. Serum IL-4, IFN-γ and PAH were measured using LINCOplex (human multiplex immunoassay kit) and HPLC respectively.
Results:
IL-4 mRNA expression was significantly increased (P < 0.05) in children with asthma compared to healthy control group whereas no differences were observed for either IFN-γ or ACSL3 mRNA. Similarly, serum IL- 4 and PAHs concentration was significantly higher as well in children with asthma in whom IFN-γ was also significantly lower. Results obtained in rats showed that exposure to the benzopyrene prototype PAH resulted in a 2.6 fold (P < 0.001) increased IL-4 mRNA expression in blood.
Conclusion:
Peripheral blood IL-4 mRNA levels, serum concentration of this cytokine are elevated in children with asthma. Also, elevated levels of PAH were observed in children with asthma. Additionally, PAH administration in rodents resulted in an increased IL-4 mRNA which is supposed to partly mediate the inflammatory response noted in asthma.
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