scholarly journals Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus

2021 ◽  
Vol 12 ◽  
Author(s):  
Wook-Joo Lee ◽  
Won-Sik Shim
Keyword(s):  
Mast Cells ◽  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Skin Barrier ◽  
Receptor Potential ◽  
Barrier Dysfunction ◽  
Dry Skin ◽  
Neuroimmune Interactions ◽  
Skin Conditions ◽  
Transient Receptor

Dry skin is a symptom of skin barrier dysfunction that evokes pruritus; however, the cutaneous neuroimmune interactions underlying dry skin-induced pruritus remain unclear. Therefore, we aimed to elucidate the mechanisms underlying dry skin-induced pruritus. To this end, an acetone/ethanol/water (AEW)-induced mouse model of dry skin was used in this study. We observed that the production of thymic stromal lymphopoietin (TSLP) significantly increased in the keratinocytes of AEW mice. Importantly, treatment with an antagonist of transient receptor potential cation channel subfamily V member 4 (TRPV4), HC067047, ameliorated dry skin conditions in AEW mice. The symptoms of dry skin were significantly reduced in Trpv4 knockout (KO) mice following treatment with AEW. The increase in the intracellular calcium levels by TSLP in the dorsal root ganglia (DRG) of Trpv4 KO mice was also significantly attenuated. The spontaneous scratching bouts were significantly decreased in both the HC067047-treated and Trpv4 KO AEW mice. Importantly, the TSLP-dependent release of tryptase from the mast cells was significantly reduced in both the HC067047-treated mice and Trpv4 KO AEW mice. Notably, inhibition of the TSLP-induced signaling pathway in DRG selectively reduced the spontaneous scratching bouts in AEW mice. Overall, the results demonstrated that the cutaneous neuroimmune interactions of TSLP and TRPV4 play pivotal roles in dry skin-induced pruritus.

scholarly journals The Role of Transient Receptor Potential A1 and G Protein-Coupled Receptor 39 in Zinc-Mediated Acute and Chronic Itch in Mice

2022 ◽  
Vol 14 ◽  
Author(s):  
Yue Hu ◽  
Qing-Yue Fu ◽  
Dan-Ni Fu ◽  
Xue-Long Wang ◽  
Zhi-Hong Wang ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Systemic Administration ◽  
Common Symptom ◽  
Dry Skin ◽  
C Fibers ◽  
Transient Receptor Potential A1 ◽  
Chronic Itch ◽  
Transient Receptor

Itching is a common symptom of many skin or systemic diseases and has a negative impact on the quality of life. Zinc, one of the most important trace elements in an organism, plays an important role in the regulation of pain. Whether and how zinc regulates itching is largely unclear. Herein, we explored the role of Zn2+ in the regulation of acute and chronic itch in mice. It is found that intradermal injection (i.d.) of Zn2+ dose-dependently induced acute itch and transient receptor potential A1 (TRPA1) participated in Zn2+-induced acute itch in mice. Moreover, the pharmacological analysis showed the involvement of histamine, mast cells, opioid receptors, and capsaicin-sensitive C-fibers in Zn2+-induced acute itch in mice. Systemic administration of Zn2+ chelators, such as N,N,N′,N′-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), pyrithione, and clioquinol were able to attenuate both acute itch and dry skin-induced chronic itch in mice. Quantitative polymerase chain reaction (Q-PCR) analysis showed that the messenger RNA (mRNA) expression levels of zinc transporters (ZIPs and ZnTs) significantly changed in the dorsal root ganglia (DRG) under dry skin-induced chronic itch condition in mice. Activation of extracellular signal-regulated kinase (ERK) pathway was induced in the DRG and skin by the administration of zinc or under dry skin condition, which was inhibited by systemic administration of Zn2+ chelators. Finally, we found that the expression of GPR39 (a zinc-sensing GPCR) was significantly upregulated in the dry skin mice model and involved in the pathogenesis of chronic itch. Together, these results indicated that the TRPA1/GPR39/ERK axis mediated the zinc-induced itch and, thus, targeting zinc signaling may be a promising strategy for anti-itch therapy.

scholarly journals Mucin-mimetic action of capsaicin improves high fat diet-induced gut barrier dysfunction in mice colon

2021 ◽  
Author(s):  
Vijay Kumar ◽  
Vibhu Kumar ◽  
Neha Mahajan ◽  
Jasleen Kaur ◽  
Kirti Devi ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Barrier Dysfunction ◽  
Gut Barrier ◽  
Mucus Production ◽  
Diet Induced Obesity ◽  
Transient Receptor ◽  
Junction Proteins

The gut barrier, including tight junction proteins and mucus layers, is the first line of defense against physical, chemical, or pathogenic incursions. This barrier is compromised in various health disorders. Capsaicin, a dietary agonist of Transient receptor potential vanilloid 1 (TRPV1) channel, is reported to alleviate the complications of obesity. While its mode of action is well established to enhance energy expenditure, metabolism and prevent dysbiosis, the more local effects on the host gut, particularly the gut barrier and mucus system remain elusive. We employed a diet-induced obesity model to investigate the effect of capsaicin on the gut barrier and mucus production and to understand the involvement of mucus, bacteria, and TRPV1 in these phenomena. Mucin feeding reflected most of the effects produced by capsaicin, indicating that mucus modulation by capsaicin plays a crucial role in its anti-obesity effects. Capsaicin, bacteria and the host mucus system seem to act in a cyclic cascade involving TRPV1, which can be activated by capsaicin and various bacteria. These findings provide new insight into the role of TRPV1 in maintaining a healthy gut environment.

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