Ciclosporin modulates the responses of canine progenitor epidermal keratinocytes (CPEK) to toll-like receptor agonists

Hendricks, Anke; Elson-Riggins, Jocelyn G.; Riddle, Anna; House, A. K.; Varjonen, Katarina; Bond, Robert P.

doi:10.1016/j.vetimm.2012.03.010

Cited by 13 publications

(16 citation statements)

References 32 publications

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“…The pattern recognition receptors (PRRs) and their signaling cascades are one way keratinocytes can detect potential pathogens and initiate an antiviral immune response (Tohyama et al, 2005; Lebre et al, 2007; Sugita et al, 2007; Kalali et al, 2008; Miller, 2008; Prens et al, 2008; Hendricks et al, 2012). Viral recognition by these PRRs initiates signaling cascades that lead to the production of type I IFNs and proinflammatory cytokines, which are important for the elimination of viruses (Barbalat et al, 2011; Rathinam and Fitzgerald, 2011).…”

Section: Introductionmentioning

confidence: 99%

Canine keratinocytes upregulate type I interferons and proinflammatory cytokines in response to poly(dA:dT) but not to canine papillomavirus

Luff

Yuan

Suter

et al. 2013

Veterinary Immunology and Immunopathology

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Papillomaviruses (PV) are double stranded (ds) DNA viruses that infect epithelial cells within the skin or mucosa, most often causing benign neoplasms that spontaneously regress. The immune system plays a key role in the defense against PVs. Since these viruses infect keratinocytes, we wanted to investigate the role of the keratinocyte in initiating an immune response to canine papillomavirus-2 (CPV-2) in the dog. Keratinocytes express a variety of pattern recognition receptors (PRR) to distinguish different cutaneous pathogens and initiate an immune response. We examined the mRNA expression patterns for several recently described cytosolic nucleic acid sensing PRRs in canine monolayer keratinocyte cultures using quantitative reverse transcription-polymerase chain reaction. Unstimulated normal cells were found to express mRNA for melanoma differentiation associated gene 5 (MDA5), retinoic acid-inducible gene I (RIG-I), DNA-dependent activation of interferon regulatory factors, leucine rich repeat flightless interacting protein 1, and interferon inducible gene 16 (IFI16), as well as their adaptor molecules myeloid differentiation primary response gene 88, interferon-β promoter stimulator 1, and endoplasmic reticulum-resident transmembrane protein stimulator of interferon genes. When stimulated with synthetic dsDNA [poly(dA:dT)] or dsRNA [poly(I:C)], keratinocytes responded with increased mRNA expression levels for interleukin-6, tumor necrosis factor-α, interferon-β, RIG-I, IFI16, and MDA5. There was no detectable increase in mRNA expression, however, in keratinocytes infected with CPV-2. Furthermore, CPV-2-infected keratinocytes stimulated with poly(dA:dT) and poly(I:C) showed similar mRNA expression levels for these gene products when compared with expression levels in uninfected cells. These results suggest that although canine keratinocytes contain functional PRRs that can recognize and respond to dsDNA and dsRNA ligands, they do not appear to recognize or initiate a similar response to CPV-2.

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Section: Introductionmentioning

confidence: 99%

Canine keratinocytes upregulate type I interferons and proinflammatory cytokines in response to poly(dA:dT) but not to canine papillomavirus

Luff

Yuan

Suter

et al. 2013

Veterinary Immunology and Immunopathology

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“…Our study showed that CPEKs did not secrete any detectable monocyte chemotactic protein‐1, but did secrete low levels of TNFα, IFNγ, IL‐15, GM‐CSF, IL‐6, IL‐7 and IL‐10. The mRNA of TNFα, a very powerful pro‐inflammatory cytokine, has previously been detected in CPEKs, but only after stimulation with atopic allergens . These various cytokines have also been found, although usually only at the mRNA level, in skin lesions or skin cell lines, including canine samples, stimulated with allergenic agents .…”

Section: Discussionmentioning

confidence: 99%

Canine progenitor epidermal keratinocytes express various inflammatory markers, including interleukin‐8 and CD40, which are affected by certain antibiotics

White

Wolsic

Campbell

et al. 2014

Veterinary Dermatology

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“…However, GM‐CSF production induced by papain was not completely but partly suppressed by ciclosporin, suggesting that its transcription was regulated not only by NFAT but also by other pathways, such as NF‐κB . A recent study indicated that ciclosporin induced Toll‐like receptor 2‐mediated TNF‐α transcription in CPEK cells, which was most probably associated with NF‐κB activation . It has been shown that Toll‐like receptor‐mediated NF‐κB activation was negatively regulated by calcineurin .…”

Section: Discussionmentioning

confidence: 99%

Involvement of nuclear factor of activated T cells in granulocyte–macrophage colony‐stimulating factor production in canine keratinocytes stimulated with a cysteine protease

Kimura

Sekido

Iio

et al. 2013

Veterinary Dermatology

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Ciclosporin modulates the responses of canine progenitor epidermal keratinocytes (CPEK) to toll-like receptor agonists

Cited by 13 publications

References 32 publications

Canine keratinocytes upregulate type I interferons and proinflammatory cytokines in response to poly(dA:dT) but not to canine papillomavirus

Canine keratinocytes upregulate type I interferons and proinflammatory cytokines in response to poly(dA:dT) but not to canine papillomavirus

Canine progenitor epidermal keratinocytes express various inflammatory markers, including interleukin‐8 and CD40, which are affected by certain antibiotics

Involvement of nuclear factor of activated T cells in granulocyte–macrophage colony‐stimulating factor production in canine keratinocytes stimulated with a cysteine protease

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