A mouse model for vitamin D-induced human cathelicidin antimicrobial peptide gene expression

Lowry, Malcolm B.; Guo, Cheng; Zhang, Yang; Fantacone, Mary L.; Logan, Isabelle E.; Campbell, Yan L.; Zhang, Weijian; Le, Mai; Indra, Arup K.; Ganguli‐Indra, Gitali; Xie, Jingwei; Gallo, Richard L.; Koeffler, H. Phillip; Gombart, Adrian F.

doi:10.1016/j.jsbmb.2019.105552

Cited by 29 publications

(21 citation statements)

References 77 publications

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“…Our data instead showed that both treatments are potent inducers of antimicrobial defensins, namely Defb1, Defb3 and Defb4. These results corroborate previous reports on calcipotriol- 45,46 and oxazolone-induced AD models, 21 displaying increased AMP levels. Interestingly, an upregulation of hBD-2 and hBD-3 has been reported in human acute AD lesions compared with healthy skin 47 or to chronic AD lesions.…”

Section: Discussionsupporting

confidence: 93%

Microbial dysbiosis in a mouse model of atopic dermatitis mimics shifts in human microbiome and correlates with the key pro‐inflammatory cytokines IL‐4, IL‐33 and TSLP

Amar

Schneider

Köberle

et al. 2022

Acad Dermatol Venereol

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Background Cutaneous bacterial dysbiosis is a characteristic hallmark of atopic dermatitis (AD), and it decisively influences the severity of the disease. Despite this, frequently used murine models of AD have not been characterized regarding the changes in skin microbiome communities.Objective To analyse the skin microbiome of two frequently used murine models for AD for assessing their applicability in translational research.Methods AD was induced in mice by topical application of calcipotriol or oxazolone. Following comparable elicitation of AD-like dermatitis, including IgE induction, the skin microbial communities were analysed and compared with human AD. ResultsWe detected critical differences in the microbiota composition of diseased skin. In contrast to calcipotriol treatment, application of oxazolone induced significant changes in the cutaneous microbiota and a drastic drop of bacterial richness. Furthermore, an expansion of Staphylococci, particularly S. xylosus, was observed in the oxazolone group, also displaying positive correlations with AD key markers including pH, TEWL, IL-4, TSLP and IL-33. ConclusionsIn this article, we show that (a) the model of choice to investigate AD needs to be characterized for the cutaneous microbiota if applicable and (b) the oxazolone-mediated mixed Th1-Th2 immune response triggers microbiota-induced alterations which share similarities to dysbiosis in human AD and represents therefore a suitable model for translational research on AD if alterations of the microbiome are in the focus of the investigation.

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Section: Discussionsupporting

confidence: 93%

Microbial dysbiosis in a mouse model of atopic dermatitis mimics shifts in human microbiome and correlates with the key pro‐inflammatory cytokines IL‐4, IL‐33 and TSLP

Amar

Schneider

Köberle

et al. 2022

Acad Dermatol Venereol

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“…Recently, a transgenic mice that carries a genomic DNA fragment encompassing the entire human CAMP gene was generated (93). In this study, topically applied 1,25(OH) 2 D 3 induced CAMP expression and boosted Staphylococcus aureus killing.…”

Section: Positive Correlation Between Circulating Cathelicidin and 25mentioning

confidence: 93%

The roles of vitamin D and cathelicidin in type 1 diabetes susceptibility

Cristelo

Machado

Sarmento

et al. 2021

Endocrine Connections

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Type 1 diabetes has increasingly greater incidence and prevalence with no cure available. Vitamin D supplementation is well documented to reduce the risk of developing type 1 diabetes. Being involved in the modulation of cathelicidin expression, the question whether cathelicidin may be one of the underlying cause arises. Cathelicidin has been implicated in both the development and the protection against type 1 diabetes by mediating the interplay between the gut microbiome, the immune system and β cell function. While its potential on type 1 diabetes treatment seems high, the understanding of its effects is still limited. This review aims to contribute to a more comprehensive understanding of the potential of vitamin D and cathelicidin as adjuvants in type 1 diabetes therapy.

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“…Cathelicidins have broad spectrum antimicrobial activity and are constitutively expressed by follicular keratinocytes and mast cells in healthy skin. The production of LL-37 is induced by cutaneous inflammation, often at the hands of pathogens ( 10 , 38 , 39 ). LL-37 is also present in sweat and wound fluid ( 38 , 78 ).…”

Section: The Role Of Amps In Hs Pathologymentioning

confidence: 99%

Innate immunity and microbial dysbiosis in hidradenitis suppurativa – vicious cycle of chronic inflammation

et al. 2022

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Hidradenitis Suppurativa (HS) is a chronic multifactorial inflammatory skin disease with incompletely understood mechanisms of disease pathology. HS is characterized by aberrant activation of the innate immune system, resulting in activation of pathways that aim to protect against pathogenic microorganisms, and also contribute to failure to resolve inflammation. Imbalance in innate immunity is evident in deregulation of host antimicrobial peptides (AMPs) and the complement system associated with the microbiome dysbiosis. The pathology is further complicated by ability of pathogens associated with HS to overcome host immune response. Potential roles of major AMPs, cathelicidin, defensins, dermcidin, S100 proteins, RNAse 7 and complement proteins are discussed. Dysregulated expression pattern of innate immunity components in conjunction with bacterial component of the disease warrants consideration of novel treatment approaches targeting both host immunity and pathogenic microbiome in HS.

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A mouse model for vitamin D-induced human cathelicidin antimicrobial peptide gene expression

Cited by 29 publications

References 77 publications

Microbial dysbiosis in a mouse model of atopic dermatitis mimics shifts in human microbiome and correlates with the key pro‐inflammatory cytokines IL‐4, IL‐33 and TSLP

Microbial dysbiosis in a mouse model of atopic dermatitis mimics shifts in human microbiome and correlates with the key pro‐inflammatory cytokines IL‐4, IL‐33 and TSLP

The roles of vitamin D and cathelicidin in type 1 diabetes susceptibility

Innate immunity and microbial dysbiosis in hidradenitis suppurativa – vicious cycle of chronic inflammation

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