Cathepsin E induces itch-related response through the production of endothelin-1 in mice

Andoh, Tsugunobu; Yoshida, Tetsuro; Lee, Jung‐Bum; Kuraishi, Yasushi

doi:10.1016/j.ejphar.2012.04.024

Cited by 19 publications

(9 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cathepsins are lysosomal proteinases that function primarily in protein turnover in the lysosome (Kuester et al, 2008). However, additional roles for cathepsins include (but are not limited to) antigen presentation (Yamamoto et al, 2012), keratinocyte differentiation (Yamamoto et al, 2012), itch responses (Andoh et al, 2012), and wound healing (Akira and Takeda, 2004). The chemotaxis cluster contained chemokines Ccl24, Ccl17, Ccl5, Ccl4, Ccl8, Ccl3, and Cxcl16 consistent with the migration of lymphocytes, monocytes, neutrophils, eosinophils, and basophils into the bite site.…”

Section: Resultsmentioning

confidence: 99%

Murine cutaneous responses to the rocky mountain spotted fever vector, Dermacentor andersoni, feeding

et al. 2014

View full text Add to dashboard Cite

Tick salivary glands produce complex cocktails of bioactive molecules that facilitate blood feeding and pathogen transmission by modulating host hemostasis, pain/itch responses, wound healing, and both innate and adaptive immunity. In this study, cutaneous responses at Dermacentor andersoni bite-sites were analyzed using Affymetrix mouse genome arrays and histopathology at 12, 48, 96 and 120 h post-infestation (hpi) during primary infestations and 120 hpi during secondary infestations. The microarray data suggests: (1) chemotaxis of neutrophils, monocytes, and other cell types; (2) production and scavenging of reactive oxygen species; and, (3) keratin-based wound healing responses. Histological analysis supported the microarray findings. At 12 hpi, a mild inflammatory infiltrate was present in the dermis, especially concentrated at the junction between dermal connective tissue and underlying adipose tissue. A small lesion was located immediately under the hypostome and likely represents the feeding "pool." Surprisingly, at 48 hpi, the number of inflammatory cells had not increased from 12 hpi, perhaps mirroring the reduction in gene expression seen at this time point. The feeding lesion is very well defined, and extravasated erythrocytes are readily evident around the hypostome. By 96 hpi, the inflammatory infiltrate has increased dramatically and the feeding lesion appears to have moved deeper into the dermis. At 120 hpi, most of the changes at 96 hpi are intensified. The infiltrate is very dense, the epidermis is markedly thickened, the feeding lesion is poorly defined and the dermal tissue near the hypostome appears to be loosing its normal architecture. In conclusion, during D. andersoni feeding infiltration of inflammatory cells increases across time concurrent with significant changes in the epidermal and dermal compartments near the feeding tick. The importance of changes in the epidermal layer in the host response to ticks is not known, however, it is possible the host attempts to "slough off" the tick by greatly increasing epithelial cell replication.

show abstract

Section: Resultsmentioning

confidence: 99%

Murine cutaneous responses to the rocky mountain spotted fever vector, Dermacentor andersoni, feeding

et al. 2014

View full text Add to dashboard Cite

show abstract

“…One possibility is that BAM8–22 might elicit self-sensitization indirectly via the activation of non-neuronal cells such as keratinocytes. Keratinocytes produce a variety of mediators that induce or enhance itch, such as leukotriene B4, endothelin-1 and NO (Andoh et al 2001; Andoh and Kuraishi 2003; Andoh et al 2012). BAM8–22 is unlikely to act at mast cells, since a recent human study reported that intradermal injection of BAM8–22 elicited itch that was not significantly affected by an antihistamine, and was not accompanied by flare (Sikand et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Cross-sensitization of histamine-independent itch in mouse primary sensory neurons

et al. 2012

View full text Add to dashboard Cite

Overexpression of pruritogens and their precursors may contribute to the sensitization of histamine-dependent and –independent itch-signaling pathways in chronic itch. We presently investigated self- and cross-sensitization of scratching behavior elicited by various pruritogens, and their effects on primary sensory neurons. The MrgprC11 agonist BAM8–22 exhibited self- and reciprocal cross-sensitization of scratching evoked by the protease-activated receptor-2 (PAR-2) agonist SLIGRL. The MrgprA3 agonist chloroquine unidirectionally cross-sensitized BAM8–22-evoked scratching. Histamine unidirectionally cross-sensitized scratching evoked by chloroquine and BAM8–22. SLIGRL unidirectionally cross-sensitized scratching evoked by chloroquine. Dorsal root ganglion (DRG) cells responded to various combinations of pruritogens and algogens. Neither chloroquine, BAM8–22 nor histamine had any effect on responses of DRG cell responses to subsequently applied pruritogens, implying that their behavioral self- and cross-sensitization effects are mediated indirectly. SLIGRL unilaterally cross-sensitized responses of DRG cells to chloroquine and BAM8–22, consistent with the behavioral data. These results indicate that unidirectional cross-sensitization of histamine-independent itch-signaling pathways might occur at a peripheral site through PAR-2. PAR-2 expressed in pruriceptive nerve endings is a potential target to reduce sensitization associated with chronic itch.

show abstract

“…Because ET-1 causes a wheal-and-flare response in human skin, it is possible that it evokes the itch sensation by inducing the release of endogenous itch mediators (e.g., histamine) from mast cells. In a recent study (8), researchers found that ET-1 is involved in the itch sensation induced by cathepsin E, an aspartic protease. The ET A antagonist blocked the scratching behavior that was induced by intradermal injection of cathepsin E. They also observed increased ET-1 levels in the skin at the injection site, leading to the hypothesis that cathepsin E induces the release of ET-1 in vivo to evoke the itch sensation.…”

Section: Peripheral Itch Mediators and Related Receptorsmentioning

confidence: 99%

Itch Mechanisms and Circuits

Han

Dong²

2014

Annu. Rev. Biophys.

147

121

View full text Add to dashboard Cite

The itch-scratch reflex serves as a protective mechanism in everyday life. However, chronic persistent itching can be devastating. Despite the clinical importance of the itch sensation, its mechanism remains elusive. In the past decade, substantial progress has been made to uncover the mystery of itching. Here, we review the molecules, cells, and circuits known to mediate the itch sensation, which, coupled with advances in understanding the pathophysiology of chronic itching conditions, will hopefully contribute to the development of new anti-itch therapies.

show abstract

Cathepsin E induces itch-related response through the production of endothelin-1 in mice

Cited by 19 publications

References 41 publications

Murine cutaneous responses to the rocky mountain spotted fever vector, Dermacentor andersoni, feeding

Murine cutaneous responses to the rocky mountain spotted fever vector, Dermacentor andersoni, feeding

Cross-sensitization of histamine-independent itch in mouse primary sensory neurons

Itch Mechanisms and Circuits

Contact Info

Product

Resources

About