Infliximab in the treatment of moderate to severe atopic dermatitis

Jacobi, Arnd; Antoni, Christian; Manger, Bernhard; Schuler, Gerold; Hertl, Michael

doi:10.1016/j.jaad.2004.11.022

Cited by 174 publications

(122 citation statements)

References 16 publications

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“…It is well-known that the Th2 cytokines, IL-4 and IL-13, play a crucial role in the pathogenesis of atopic dermatitis, as well as in ACD (12)(13)(14). In addition to IL-4 and IL-13, TNF-a has also been suggested to play some role in the pathogenesis of these disorders (41)(42)(43). Therefore, it is conceivable that ROS generated by TNF-a and Th2 cytokines may synergistically stimulate epidermal STAT6 signaling via upregulation of NOX/DUOX family members in these inflammatory skin disorders.…”

Section: Discussionmentioning

confidence: 99%

Dual Oxidase 1 Induced by Th2 Cytokines Promotes STAT6 Phosphorylation via Oxidative Inactivation of Protein Tyrosine Phosphatase 1B in Human Epidermal Keratinocytes

Hirakawa

Saito

Ohara

et al. 2011

The Journal of Immunology

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Although hydrogen peroxide (H2O2) is better known for its cytotoxic effects, in recent years it has been shown to play a crucial role in eukaryotic signal transduction. In respiratory tract epithelial cells, the dual oxidase (DUOX) proteins 1 and 2 has been identified as the cellular source of H2O2. However, the expression of DUOX1 or DUOX2 has not yet been examined in keratinocytes. In this study, using a DNA microarray, we demonstrated that, of the seven NOX/DUOX family members in normal human epidermal keratinocytes (NHEK), IL-4/IL-13 treatment augments the expression of only DUOX1 mRNA. We next confirmed the IL-4/IL-13 induction of DUOX1 in NHEK at the mRNA and protein level using quantitative real-time PCR and Western blotting, respectively. In addition, we demonstrated that this augmented DUOX1 expression was accompanied by increased H2O2 production, which was significantly suppressed both by diphenyleneiodonium, an inhibitor of NADPH oxidase, and by small interfering RNA against DUOX1. Finally, we demonstrated that the increased expression of DUOX1 in IL-4/IL-13–treated NHEK augments STAT6 phosphorylation via oxidative inactivation of protein tyrosine phosphatase 1B. These results revealed a novel role of IL-4/IL-13–induced DUOX1 expression in making a positive feedback loop for IL-4/IL-13 signaling in keratinocytes.

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Section: Discussionmentioning

confidence: 99%

Dual Oxidase 1 Induced by Th2 Cytokines Promotes STAT6 Phosphorylation via Oxidative Inactivation of Protein Tyrosine Phosphatase 1B in Human Epidermal Keratinocytes

Hirakawa

Saito

Ohara

et al. 2011

The Journal of Immunology

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“…Nevertheless, some recent case reports have suggested the successful use of omalizumab in selected patients. Infliximab (anti-TNF-α) has been also reported to be successful in some reports 95,96 . However, one has to keep in mind that side effects of biologics may be serious and need further evaluation.…”

Section: ) Biologicsmentioning

confidence: 99%

Atopic Dermatitis

2010

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“…Like siblings, both skin conditions are characterized by intriguing similarities and distinct features at the same time. In the era of more and more specific biologic therapies, differential diagnosis becomes important, as therapeutic outcomes, for example, with anti-TNF-a antibodies, might be inefficient or even antipodal if eczema is misdiagnosed as psoriasis [1].…”

mentioning

confidence: 99%