Increased serum human β-defensin-2 levels in atopic dermatitis: Relationship to IL-22 and oncostatin M

Kanda, Naoko; Watanabe, Shinichi

doi:10.1016/j.imbio.2011.10.010

Cited by 58 publications

(50 citation statements)

References 44 publications

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“…Members of the third group, for example, hBD-2, hBD-3, and LL-37, are only detectable in inflamed skin (2,(77)(78)(79). Increased amounts of the AMPs psoriasin, RNase-7, hBD-2, and hBD-3 were found in lesional and nonlesional skin and fluids obtained in washings from the skin of AD patients compared with healthy controls (2,5,(80)(81)(82)(83)(84). This finding seems to be at odds with the observations of increased superinfection with bacteria in patients suffering from AD (5,8,9,85,86).…”

Section: Discussionmentioning

confidence: 99%

Control of the Physical and Antimicrobial Skin Barrier by an IL-31–IL-1 Signaling Network

Hänel

Pfaff

Cornelissen

et al. 2016

The Journal of Immunology

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Atopic dermatitis, a chronic inflammatory skin disease with increasing prevalence, is closely associated with skin barrier defects. A cytokine related to disease severity and inhibition of keratinocyte differentiation is IL-31. To identify its molecular targets, IL-31–dependent gene expression was determined in three-dimensional organotypic skin models. IL-31–regulated genes are involved in the formation of an intact physical skin barrier. Many of these genes were poorly induced during differentiation as a consequence of IL-31 treatment, resulting in increased penetrability to allergens and irritants. Furthermore, studies employing cell-sorted skin equivalents in SCID/NOD mice demonstrated enhanced transepidermal water loss following s.c. administration of IL-31. We identified the IL-1 cytokine network as a downstream effector of IL-31 signaling. Anakinra, an IL-1R antagonist, blocked the IL-31 effects on skin differentiation. In addition to the effects on the physical barrier, IL-31 stimulated the expression of antimicrobial peptides, thereby inhibiting bacterial growth on the three-dimensional organotypic skin models. This was evident already at low doses of IL-31, insufficient to interfere with the physical barrier. Together, these findings demonstrate that IL-31 affects keratinocyte differentiation in multiple ways and that the IL-1 cytokine network is a major downstream effector of IL-31 signaling in deregulating the physical skin barrier. Moreover, by interfering with IL-31, a currently evaluated drug target, we will have to consider that low doses of IL-31 promote the antimicrobial barrier, and thus a complete inhibition of IL-31 signaling may be undesirable.

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Section: Discussionmentioning

confidence: 99%

Control of the Physical and Antimicrobial Skin Barrier by an IL-31–IL-1 Signaling Network

Hänel

Pfaff

Cornelissen

et al. 2016

The Journal of Immunology

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“…Moreover, IL-22 was detected in a greater number of patients and the serum level was about 3-fold higher than that in controls (Figure 2). In CD3/28-stimulated T cells, hBD-2 increases IL-22 production, which, in turn, Controls 2 3 4 5 6.7 2 3 4 5 6.7 2 3 4 5 6 .7 2 3 4 5 6.7 2 3 4 5 6.7 Tinea unguium induces hBD-2 expression through the Jak signal transducer and activator of transcription (Jak-STAT) signaling pathway (Aujla et al, 2008;Kanda and Watanabe, 2012). Furthermore, IL-22 activates STAT3 in keratinocytes, whereas loss of STAT3 expression abrogated the inductive effect of IL-22 on genes that regulate keratinocyte differentiation (Wolk et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…It was suggested that STAT3 expression enhances the sensitivity of keratinocytes to subsequent IL-22 exposure, thus providing regulatory control through positive feedback. IL-22 expression is reported to be induced by NF-kB, CCAAT/enhancer-binding protein (C/EBP), or specificity protein 1 (Sp1); hBD-2-induced extracellular signal-regulated kinase stimulates IL-22 production by activating Sp1 and C/EBP expression and/or inducing their phosphorylation (Kanda and Watanabe, 2012). It was therefore speculated that altered serum IL-22 level is associated with DEFB4 CN variation, which was examined in this study.…”

Section: Discussionmentioning

confidence: 99%

Low DEFB4 Copy Number and High Systemic hBD-2 and IL-22 Levels Are Associated with Dermatophytosis

Jaradat

Cubillos

Krieg

et al. 2015

Journal of Investigative Dermatology

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Dermatophytes initiate dermatophytosis, but susceptibility to infection is dictated by host genetic factors, although the role of some of these-such as human beta-defensin 2 (hBD-2) genomic (DEFB4) copy number (CN) variation and its induction by IL-22-remains unclear. This was investigated in this cross-sectional study in 442 unrelated Caucasian subjects, including 195 healthy controls and 247 dermatophytosis patients who were divided into five subgroups according to clinical presentation. DNA samples were evaluated for DEFB4 CN variation by relative quantification using the comparative CT method, and serum hBD-2 and IL-22 levels were determined by ELISA. DEFB4 CN in patients was significantly lower and, except in the tinea cruris subgroup, serum hBD-2 levels were higher than in controls. The positive correlation between hBD-2 levels and DEFB4 CN observed in controls was not detected in patients, who also had higher serum IL-22 levels that were positively correlated with hBD-2 levels. Moreover, unlike in control subjects, the serum IL-22 level was negatively correlated with DEFB4 CN in patients. Taken together, these findings suggest an association between decreased DEFB4 CN, elevated serum hBD-2 and IL-22 levels, and dermatophytosis, underscoring a gene/cytokine interaction in the occurrence of this infection.

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“…A recent investigation by Kanda et al showed that hBD-2 and hBD-3 enable keratinocytes to produce the Th2 cytokines IL-4, IL-13 and IL-31 109) . Furthermore, our group has demonstrated that hBD-2, hBD-3, hBD-4 and LL-37 induce mast cell degranulation and the production of PGD2, PGE2, leukotriene C4 and IL-31 19)-21) .…”

Section: Amps/hdps In Admentioning

confidence: 99%

Novel Insight Into the Role of Antimicrobial (Host Defense) Peptides/Proteins in Human Skin Diseases

Niyonsaba

2016

Juntendo Medical Journal

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In addition to functioning as a physical barrier, the skin has evolved several innate defense mechanisms for the rapid recognition of and protection against harmful microorganisms. As a part of this process, the skin releases a vast and powerful arsenal of antimicrobial peptides/proteins (AMPs), also called host defense peptides/proteins (HDPs), which are key players in the cutaneous immune system. Although originally named antimicrobial peptides, recent evidence has demonstrated that AMPs/HDPs play additional roles in orchestrating the adaptive immune response, such as the regulation of inflammation, induction of cell proliferation and differentiation, regulation of cytokine/chemokine production, facilitation of cell migration, promotion of wound healing and regulation of tight junction barriers. Additionally, numerous skin diseases show altered expression of AMPs/HDPs in the lesional skin, suggesting the crucial roles of these molecules in the pathophysiology of skin diseases. The purpose of this review is to describe the current knowledge regarding some of the most common and well-known AMPs/HDPs derived from the skin, to discuss the regulation of their expression and their antimicrobial and immunomodulatory functions, and to outline their roles in various skin diseases. We believe that understanding the basic knowledge of skin-derived AMPs/HDPs would provide new insight into the pathophysiology of skin disorders and offer novel therapeutic opportunities for skin infectious diseases.

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Increased serum human β-defensin-2 levels in atopic dermatitis: Relationship to IL-22 and oncostatin M

Cited by 58 publications

References 44 publications

Control of the Physical and Antimicrobial Skin Barrier by an IL-31–IL-1 Signaling Network

Control of the Physical and Antimicrobial Skin Barrier by an IL-31–IL-1 Signaling Network

Low DEFB4 Copy Number and High Systemic hBD-2 and IL-22 Levels Are Associated with Dermatophytosis

Novel Insight Into the Role of Antimicrobial (Host Defense) Peptides/Proteins in Human Skin Diseases

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