Protease-activated receptor-2 induces proinflammatory cytokine and chemokine gene expression in canine keratinocytes

Maeda, Shingo; Maeda, Sadatoshi; Ohno, Koichi; Kaji, Noriyuki; Hori, Masaru; Fujino, Yasuhito; Tsujimoto, Hajime

doi:10.1016/j.vetimm.2013.01.018

Cited by 23 publications

(46 citation statements)

References 37 publications

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“…The sections were blocked with 5% skim milk in Tris-buffered saline (TBS) at room temperature for 60 min and then incubated with a mouse anti-human PAR-2 mAb (SAM 11; Santa Cruz Biotechnology, Santa Cruz, CA, U.S.A.) at 4°C overnight. The cross-reactivity of this mAb with canine PAR-2 was confirmed in a previous study [26]. The slides were washed with TBS and then incubated with EnVision polymer reagent (Dako) at room temperature for 45 min.…”

Section: Methodssupporting

confidence: 57%

“…After pre-incubation, the tissues were exposed to 25 U/m l trypsin (Wako Pure Chemical Industries, Osaka, Japan), 250 µ M human PAR-2 agonist peptide (SLIGKV-NH 2 ; Bachem, Bubendorf, Switzerland) or 250 µ M inverse control peptide (LSIGKV-NH 2 ; Bachem) to activate PAR-2. The ability of the human PAR-2 agonist to activate canine PAR-2 was confirmed in a previous study [26]. HBSS alone was added to the tissues of each dog as an “unstimulated” control.…”

Section: Methodsmentioning

confidence: 60%

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Intestinal Protease-Activated Receptor-2 and Fecal Serine Protease Activity are Increased in Canine Inflammatory Bowel Disease and May Contribute to Intestinal Cytokine Expression

Maeda

Ohno

Uchida

et al. 2014

The Journal of Veterinary Medical Science

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Serine proteases elicit cellular responses via protease-activated receptor-2 (PAR-2) which is known to regulate inflammation and the immune response. Although the gastrointestinal tract is exposed to large amounts of proteolytic enzymes, the role of PAR-2 in canine inflammatory bowel disease (IBD) remains unclear. The objective of this study was to investigate the effects of PAR-2 activation on inflammatory cytokine/chemokine gene expression in canine intestine and the expression of intestinal PAR-2 and fecal serine protease activity in dogs with IBD. Duodenal biopsies from healthy dogs were cultured and treated ex vivo with trypsin or PAR-2 agonist peptide, and inflammatory cytokine/chemokine gene expression in the tissues was then quantified by real-time PCR. PAR-2 mRNA and protein expression levels in the duodenal mucosa were examined by real-time PCR and immunohistochemistry, respectively. Fecal serine protease activity was determined by azocasein assay. In ex vivo-cultured duodenum, trypsin and PAR-2 agonist peptide induced significant up-regulation of mRNA expression levels of interleukin-1 β (IL-1β), IL-8, mucosae-associated epithelial chemokine (MEC) and fractalkine, and this up-regulation was inhibited by a serine protease inhibitor. Duodenal PAR-2 mRNA and protein expression levels were higher in dogs with IBD than in healthy control dogs. Fecal serine protease activity was significantly elevated in dogs with IBD, and the level of activity correlated positively with the clinical severity score. These results suggest that PAR-2 may contribute to the pathogenesis of canine IBD by inducing expression of inflammatory mediators in response to luminal serine proteases.

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Section: Methodssupporting

confidence: 57%

Section: Methodsmentioning

confidence: 60%

Intestinal Protease-Activated Receptor-2 and Fecal Serine Protease Activity are Increased in Canine Inflammatory Bowel Disease and May Contribute to Intestinal Cytokine Expression

Maeda

Ohno

Uchida

et al. 2014

The Journal of Veterinary Medical Science

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“…In primary tumour, however, TF may be induced by tumour cells or cells in the tumour microenvironment, such as stromal cells, monocyte, tissue macrophages and vascular endothelial cells. 28 There are two main mechanisms for TF-mediated tumour progression, depending on agglutinating substance or not. 27 In primary breast cancer, TF/FVIIa/PAR2 induces angiogenesis factors expression and immune surveillance.…”

Section: Correlation Between Monocyte Tf Level and Survivalmentioning

confidence: 99%

Role of monocyte tissue factor on patients with non‐small cell lung cancer

Deng

Zhang

et al. 2017

Clinical Respiratory J

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“…PARs belong to a subfamily of G protein‐coupled, 7‐transmembrane domain receptors, activated by specific proteolytic cleavage of their extracellular amino termini by proteases . Among PAR‐1 to ‐5, PAR‐2 has been shown to be expressed in the keratinocytes of humans, mice and dogs . Recent studies in humans and dogs have indicated that activation of TLRs and PAR‐2 in keratinocytes induces the production of cytokines and chemokines necessary for initiating and maintaining allergic inflammation.…”

Section: Cutaneous Immune Reactionsmentioning

confidence: 99%

A review of the roles of keratinocyte‐derived cytokines and chemokines in the pathogenesis of atopic dermatitis in humans and dogs

Asahina

Maeda

2016

Veterinary Dermatology

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Protease-activated receptor-2 induces proinflammatory cytokine and chemokine gene expression in canine keratinocytes

Cited by 23 publications

References 37 publications

Intestinal Protease-Activated Receptor-2 and Fecal Serine Protease Activity are Increased in Canine Inflammatory Bowel Disease and May Contribute to Intestinal Cytokine Expression

Intestinal Protease-Activated Receptor-2 and Fecal Serine Protease Activity are Increased in Canine Inflammatory Bowel Disease and May Contribute to Intestinal Cytokine Expression

Role of monocyte tissue factor on patients with non‐small cell lung cancer

A review of the roles of keratinocyte‐derived cytokines and chemokines in the pathogenesis of atopic dermatitis in humans and dogs

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