API

Event: 1712

Key Event Title

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Overproduction of IL-4 from Th2 cell

Short name

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Overproduction of IL-4

Biological Context

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Level of Biological Organization
Cellular

Cell term

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Cell term
T-helper 2 cell


Organ term

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Organ term
immune system


Key Event Components

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Process Object Action

Key Event Overview


AOPs Including This Key Event

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AOP Name Role of event in AOP
Exacerbation of SLE by activation of estrogen receptor KeyEvent

Stressors

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Taxonomic Applicability

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Life Stages

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Sex Applicability

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Key Event Description

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Th2 cells produce IL-4, which stimulates B-cells to proliferate, to switch immunoglobulin classes, and to differentiate into plasma and memory cells. The receptor for IL-4 is IL-4Rα, which expresses in B cells. IL4 also plays an important role in the development of certain immune disorders, particularly allergies and some autoimmune diseases and especially when there is Th2 polarization.


How It Is Measured or Detected

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Purified naive T cells were activated and infected with RV-Stat6:ER. The cells were cultured and expanded under Th1 culture conditions in the presence or absence of 0.3 μM 4-HT (Research Biochemicals Institute) for 2 weeks starting from days 1, 7, 14, or 21 and the cells were analyzed for cytokine (IL-4) expression by flow cytometer analysis of intracellular cytokine production or cytokine ELISA (Kurata H. 1999, Zhu J. 2001).

Single-cell suspensions of lymph nodes removed from BALB/c mice 7 days after priming with KLH absorbed to aluminium hydroxide adjuvant in the footpads, were prepared and cultured in vitro with KLH in the absence or presence of either BPA (0.1, 1, 10, 50 and/or 100 μM) or NP. After 4 days, the levels of IL-4 and IFN-γ in the cell supernatants were determined by a sandwich enzyme-linked immunosorbent assay (ELISA) and mRNA levels of IL-4, IL-6 and IL-10 in the cells were assayed by reverse transcription–polymerase chain reaction (RT–PCR) (Lee MH. 2003). To evaluate the effects of exposure to BPA in adulthood, male Leishmania major– susceptible BALB/c and –resistant C57BL/6 mice were subcutaneously injected with BPA (0.625, 1.25, 2.5 and 5 μmol) dissolved in corn oil 1 week before being infected with L. major. A single cell suspension containing splenocytes from each mouse was incubated in 24-well tissue-culture plates in RPMI 1640 medium supplemented with 10% FCS, penicillin (100 IU/mL), and streptomycin (100 μg/mL) at 37°C in a humidified atmosphere of 5% CO2 and 95% air. Cells were stimulated with L. major antigen (3 μg/mL) during the cultivation. Culture supernatants were collected 48 hr later.  Concentrations of IL-4, IL-10, IL-13, and IFN-γ in culture supernatants were determined using CBA kits (Huimin Y. 2008).

Th2 cell-related cytokine (IL-4 and -10) in BPA (50 μM)-stimulated primary cultured mouse lymphocytes were evaluated using immunoblot analysis and reverse-transcription polymerase chain reaction (RT-PCR) (Lee et al. 2010).


Domain of Applicability

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References

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  1. Kurata, H., Lee, H. J. Lee, O’Garra, A. and Arai, N. (1999). Ectopic expression of activated STAT6 induces the expression of Th2-specific cytokines and transcription factors in developing Th1 cells. Immunity 11: 677-688.
  2. Lee, M. H., Chung, S. W., Kang, B. Y., Park, J., Lee, C. H., Hwang, S. Y. and Kim, T. S. (2003). Enhanced interleukin-4 production in CD4+ T cells and elevated immunoglobulin E levels in antigen-primed mice by bisphenol A and nonylphenol, endocrine disruptors: involvement of nuclear factor-AT and Ca2+. Immunology 109(1): 76-86.
  3. Huimin, Y., Masaya, T. and Kazuo, S. (2008). Exposure to Bisphenol A Prenatally or in Adulthood Promotes TH2 Cytokine Production Associated with Reduction of CD4+CD25+ Regulatory T Cells. Environmental Health Perspective 116(4): 514–519.
  4. Lee, J. and Lim K. T. (2010). Plant-originated glycoprotein (36kDa) suppresses interleukin-4 and -10 in bisphenol A-stimulated primary cultured mouse lymphocytes. Drug and Chemical Toxicology. 33(4): 421-429.