| Project/Area Number |
23K09664
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 58020:Hygiene and public health-related: including laboratory approach
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2023-04-01 – 2026-03-31
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| Project Status |
Granted (Fiscal Year 2024)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2025: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2024: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2023: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Asthma / Obesity / Birth cohort / Adult asthma cohort / CCL18 / Immune pathways / Epidemiological studies / T2 biomarkers / adult asthma cohort / Obese asthma phenotype / Cohort studies / T2 inflammation / Experimental studies |
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| Outline of Research at the Start |
For the first time, we will show the effects of human CCL18 in the development of obese asthma and enhancement of Th2 inflammation in the general population of children and adult asthmatic patients. Additionally, a detailed mechanism of CCL18 regulation and the role of CCL18 in eosinophilic airway inflammation in obese asthma phenotypes will be addressed for the first time in experimental studies. This project is a collaboration between clinicians and epidemiologists, providing this opportunity to improve children's health by translating the findings from bench to bedside.
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| Outline of Annual Research Achievements |
1. Hokkaido Birth Cohort:
We have completed interviews and physical examinations for 700 children aged 10 years to assess allergic conditions. Parents completed the ISAAC questionnaires to evaluate symptoms of wheeze, rhinitis, and eczema. Additional data have been collected on sociodemographic characteristics, anthropometric measures, and asthma/allergies from birth to age 10. Biospecimens were collected from the children, and T2 inflammation biomarkers were measured, including blood eosinophil counts, FeNO, and total serum IgE. CCL18 genotyping and plasma CCL18 protein levels were also measured at age 10. CCL18 showed a significant positive association with childhood BMI, blood eosinophils, and FeNO.
2. Adult Asthma Cohort:
In this cohort, we observed a significant positive association between CCL18 levels and both BMI and blood leptin levels in asthma patients. CCL18 levels were also positively associated with T2 biomarkers, including blood and sputum eosinophils, FeNO, and blood periostin. CCL18 was associated with systemic inflammatory markers such as CRP and fibrinogen. Higher CCL18 levels were linked to poorer quality of life (AQLQ) and decreased pulmonary function parameters (FEV1% predicted, FEV1;/FVC ratio, and PEF).
3. Experimental Studies:
We have initiated in vitro studies to investigate the regulatory mechanisms of CCL18. Using THP-1 cells, we are treating cells with various interleukins and adipokines. We are currently measuring CCL18 mRNA expression via real-time RT-PCR and quantifying CCL18 protein production using cell culture supernatants and ELISA kits.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Our project is progressing smoothly. The epidemiological studies in both children and adults are advancing faster than anticipated. As for the experimental studies, progress is steady but somewhat slower, as THP-1 cells do not proliferate rapidly. Overall, the project is moving forward at a good pace, with meaningful and consistent progress across all components.
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| Strategy for Future Research Activity |
1.Hokkaido Birth Cohort: We will expand our analysis by measuring a comprehensive panel of biomarkers using Bio-Plex Assays (Bio-Rad), with a focus on pathway analysis. Two extensive panels will be utilized:
a) Cytokine Chemokine Panel (80 biomarkers)
b) Obesity Diabetes Panel (includes 12 biomarkers)
2. Adult Asthma Cohort:
We will examine the association between CCL18 levels and the risk of asthma exacerbation and hospitalization using a prospective study design. We will replicate the analysis in two additional independent cohorts within this fiscal year.
3. Experimental Studies: We will continue in vitro studies to investigate the regulatory pathways of CCL18 expression, aiming to better understand its mechanistic role in asthma, particularly in the context of obesity.
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