#SUWA SHIORI SKIN#

Keratinocytes cultured in low concentrations of calcium remain proliferative. In cultured keratinocytes, most differentiation-specific proteins are regulated by external calcium levels 18. Here, we examined the expression of H4 receptor mRNA during HaCaT cell differentiation in culture. These results suggest that H4 receptor expression is increased in keratinocytes following differentiation. Keratin K10-positive differentiated keratinocytes in the prickle cell and granular layers have been shown to strongly express the H4 receptor, whereas expression was weaker in K14-positive proliferating keratinocytes in the basal layer 12. The epidermis can be subdivided into the cornified layer, consisting of dead keratinocytes, followed by the prickle cell layer, granular layer and basal cell layer comprising viable keratinocytes at various stages of differentiation 17. The protective function of keratinocytes is enhanced by differentiation 16. Keratinocytes constitute about 95% of the cell mass of human epidermis 15. # P < 0.05 and # P < 0.001 compared with the corresponding value in the JNJ7777120 (-) group (Student's t-test). All results are representative of at least three separate experiments. Error bars represent means ± SD of triplicates. mRNA levels were normalized to the corresponding RPL13 mRNA levels, and the mean value in the JNJ7777120 (−)/(−) group was set to 1.0. Cells were cultured with histamine, TNF α and an H4 receptor antagonist as indicated. 1b).Įffect of the H4 receptor antagonist JNJ7777120 on the expression of IL-8 mRNA by histamine- and TNF α-treated HaCaT cells. Under this condition, expression of H4 receptors was increased in a time-dependent manner throughout the culture period (Fig. Expression of involucrin mRNA was markedly increased from days 2 to 4, indicating differentiation of keratinocytes. To evaluate HaCaT cell differentiation, we analysed the mRNA of a typical differentiation marker, involucrin (Fig. Results Increased expression of the histamine H4 receptor following differentiation In this study, we investigated expression of the H4 receptor in the HaCaT human keratinocyte cell line 14 and whether the receptor plays a role in the mRNA expression of a typical chemokine, interleukin (IL)-8, in these keratinocytes. However, there is little information regarding the expression and function of the H4 receptor in keratinocytes. There is also growing evidence that keratinocytes have an active role in the cutaneous inflammatory response by various chemokines and cytokines 13. It has also been reported that patients with AD express increased levels of the H4 receptor on peripheral blood T cells 9.Įxpression of the H4 receptor has been reported in the dermis and epidermis 10 and on primary sensory neurons 11, and the expression of the receptor may be increased in keratinocytes following differentiation 12. As mentioned above, H4 receptor antagonists could be effective for treating pruritus indeed, JNJ7777120 reduced chronic pruritus in a hapten-induced experimental model of AD 7, 8. Therefore, effective treatment of AD requires reduction in itching and consequent scratching. Pruritus is an essential feature of AD and greatly impacts quality of life.

#SUWA SHIORI SKIN#

AD is a chronic, pruritic, inflammatory skin disorder with a wide range of disease severity 6. In diseases in which the H4 receptor likely participates, including atopic dermatitis (AD), few drugs are effective for control of intractable pruritic dermatosis. Therefore, it is expected that the H4 receptor could become a novel therapeutic target of anti-itch, anti-inflammatory and anti-allergic drugs 4, 5. For example, histamine and selective H4 receptor agonists cause scratching responses in mice, and these responses are almost completely attenuated in H4 receptor-knockout mice or by pretreatment with the selective H4 receptor antagonist JNJ7777120 2, 3. Recent in vivo studies have demonstrated its involvement in pruritus and skin inflammation. The histamine H4 receptor is expressed on several hematopoietic cells and mediates immune responses and allergic reactions 1.

Suwa shiori