Overactivation of IL-4-induced activator protein-1 in atopic dermatitis

Yamazaki, Fumie; Aragane, Yoshinori; Maeda, Akira; Matsushita, Kiyomi; Ueno, Kengo; Yudate, Tatsuo; Kawada, Akira; Tezuka, Tadashi

doi:10.1016/s0923-1811(01)00171-2

Cited by 20 publications

(19 citation statements)

References 19 publications

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“…We have previously shown that AP-1 is a prominent transcription factor in T cells in response to IL-4 [4, 20]. Therefore, we next checked modulations of AP-1 activation by rolipram.…”

Section: Resultsmentioning

confidence: 99%

“…Th2-derived IL-4 is mandatory for the production of antigen-specific IgE from B cells, a best-known mediator in allergic disorders such as asthma or atopic dermatitis. Owing to the pivotal role of IL-4 in immediate allergies, we previously reported that in patients with atopic dermatitis T cell reactivity to IL-4 may play a pathogenic role [4]. In light of this view, mechanisms controlling the augmented IL-4 reactivity could be a target of pharmacological intervention.…”

Section: Introductionmentioning

confidence: 99%

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Antagonism of IL-4 Signaling by a Phosphodiesterase-4 Inhibitor, Rolipram, in Human T Cells

Markova

Niwa

Yamanishi³

et al. 2007

Int Arch Allergy Immunol

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Background: Phosphodiesterase (PDE4) inhibitors prevent breakdown of cAMP and affect the increase in cellular levels of cAMP, which is known to regulate immune cell functions. Because IL-4 plays a causal role in the pathogenesis of allergic disorders, we were interested to study the modulatory mechanisms of a PDE4 inhibitor, rolipram, in IL-4-mediated signaling in T cells. Methods: Human peripheral T cells were stimulated with IL-4 in combination with rolipram, and RT-PCR was performed using primers specific for IL-5. To monitor activation of transcription factors, immunostaining was employed. Results: Rolipram or a cAMP-analogue, 8-Br-cAMP, significantly downregulated IL-4-induced expression of IL-5 mRNA. The rolipram-induced inhibition of IL-5 mRNA was mediated by activation of protein kinase A (PKA), because rolipram-downregulated mRNA expression of IL-5 was restored by PKA inhibitors. Immunostaining revealed that rolipram interfered with IL-4-induced nuclear translocation of activator protein (AP)-1 components. Conclusions: This is the first demonstration of suppression of IL-4 signaling by PDE4 inhibitors via prevention of nuclear translocation of AP-1.

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“…We have previously shown that AP-1 is a prominent transcription factor in T cells in response to IL-4 [4, 20]. Therefore, we next checked modulations of AP-1 activation by rolipram.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antagonism of IL-4 Signaling by a Phosphodiesterase-4 Inhibitor, Rolipram, in Human T Cells

Markova

Niwa

Yamanishi³

et al. 2007

Int Arch Allergy Immunol

Self Cite

View full text Add to dashboard Cite

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“…IL-13 and IL-4 are known to induce isotype switching to IgE synthesis. IL-4 was detected immunohistochemically in several skin lesions of AD patients 55) , and that hyperreactivity plays a pathogenic role 56) . The mRNA expression of IL-4 was increased in DNCB group, whereas TJ treatment significantly suppressed IL-4 levels in DNCB-induced CD mice (Fig.…”

Section: ⅳ Discussionmentioning

confidence: 99%

Effects of Torilis japonica Extract on DNCB-induced Contact Dermatitis in BALB/c Mice

Lee¹,

Song²,

Hong³

2016

The Journal of Korean Medicine Ophthalmology and Otolaryngology

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“…IgE synthesis by B cells is regulated by Th2 cytokines, particularly IL-4 and IL-13. In humans, overproduction of IL-4 is a critical factor in AD development (22). Sensitization to an allergen reflects the allergen's ability to elicit a Th2 cell response, in which IL-4 and IL-13 drive IgE production by promoting class-switch recombination in B cells (17).…”

Section: A B C D Discussionmentioning

confidence: 99%

Suppression of 2,4-dinitrochlorobenzene-induced atopic dermatitis by extract of Bacillus Calmette-Guerin

Sun

Wang

Zhao

et al. 2013

Molecular Medicine Reports

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Abstract. Bacillus Calmette-Guerin extract (BCGE) has been proven to be clinically effective for anaphylactic disease, infectious diseases and cancer. In this study, we investigated the effect of the intramuscular application of BCGE on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD).We established an AD model in BALB/c mice by repeated local exposure of DNCB to the ear and dorsal skin. Following intramuscular application of BCGE, the ear thickness, mast cell infiltration, serum total immunoglobulin E (IgE) and histamine level were measured. In addition, levels of interleukin (IL)-4, IL-13, interferon (IFN)-γ and tumor necrosis factor (TNF)-α in the ears were assayed. BCGE reduced AD symptoms based on ear thickness, dermatitis score, histopathological analysis and serum IgE levels. In addition, BCGE inhibited mast cell infiltration into the ear and elevation of serum histamine, increased IFN-γ level and suppressed IL-4, IL-13 and TNF-α levels in the ears. Furthermore, BCGE attenuated the NF-κBp65 expression in the nuclear extract of the ear tissue. Taken together, our results demonstrated that intramuscular application of BCGE exerts beneficial effects on the symptoms of AD suggesting that BCGE may be a candidate for the treatment of AD.

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Overactivation of IL-4-induced activator protein-1 in atopic dermatitis

Cited by 20 publications

References 19 publications

Antagonism of IL-4 Signaling by a Phosphodiesterase-4 Inhibitor, Rolipram, in Human T Cells

Antagonism of IL-4 Signaling by a Phosphodiesterase-4 Inhibitor, Rolipram, in Human T Cells

Effects of Torilis japonica Extract on DNCB-induced Contact Dermatitis in BALB/c Mice

Suppression of 2,4-dinitrochlorobenzene-induced atopic dermatitis by extract of Bacillus Calmette-Guerin

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