What about physical contacts between epidermal keratinocytes and sensory neurons?

Recent studies have demonstrated that keratinocytes closely participate in sensory transduction, and therefore, intra‐epidermal free nerve endings are not exclusive transducers of pain. This discovery implies the existence of close afferent communication from keratinocytes to sensory neurons. Although reciprocal interactions between keratinocytes and intra‐epidermal free nerve endings via soluble mediators are well established, little attention has been paid to physical contacts between keratinocytes and intra‐epidermal free nerve endings. This review proposes to consider the ultrastructural and functional knowledge of these contacts, in both human skin biopsies and keratinocyte‐sensory neuron cocultures to speculate on the possible existence of synaptic contacts.     

皮肤细胞蛋白质组质谱分析方法的建立及肽质量指纹图谱的构建

目的建立人皮肤细胞蛋白质组学研究所需的质谱分析方法,并获得皮肤细胞蛋白质肽质量指纹图谱。方法体外培养人皮肤成纤维细胞与角质形成细胞,采用固相pH梯度双向凝胶电泳分离其总蛋白质,凝胶经染色后,在图谱上选取2个角质形成细胞蛋白点与1个成纤维细胞蛋白点,进行胶内酶切、基质辅助激光解吸电离飞行时间(MALDI-TOF)质谱分析鉴定。结果获得3个点的肽质量指纹图谱,经Mascot软件搜索人非冗余蛋白质数据库后,鉴定为细胞骨架Actingamma1、tubulinα2及热休克蛋白HSP70。结论皮肤细胞基质辅助激光解吸电离飞行时间(MALDI-TOF)质谱分析技术的建立为皮肤蛋白质组学的进一步研究提供手段。     

隐球菌与体外培养角质形成细胞的相互作用

目的：研究隐球菌与体外培养的角质形成细胞的相互作用。方法：检测新生隐球菌对体外培养的角质形成细胞HaCaT株（简称HaCaT细胞）的时间-浓度黏附率、通透率;检测新生隐球菌对细胞的损伤;透射电镜观察二者相互作用的超微结构。结果：新生隐球菌标准野生株B3501（简称B3501）可以对HaCaT细胞产生黏附与侵袭,黏附率与侵袭率呈现时间依赖性;同时,B3501还可以使HacaT细胞凋亡率升高,对其造成损伤,这与菌体的活力相关。超微结构可见新生隐球菌与角质形成细胞的黏附与侵袭过程。结论：活的隐球菌黏附与侵袭角质形成细胞是其感染皮肤的重要条件。进一步明确二者的相互作用对隐球菌发病机制的研究具有重要意义。     

Leptin induces secretion of pro‐inflammatory cytokines by human keratinocytes in vitro – a possible reason for increased severity of psoriasis in patients with a high body mass index

Investigations about prevalence of obesity in psoriasis patients are increased nowadays. Higher serum levels of leptin in patients with psoriasis who are overweight or obese suggest that leptin may serve as a molecular link between psoriasis and metabolic comorbidities. However, the pathological functions of leptin in psoriasis are not clearly understood. We investigated the influence of being overweight or obese on the risk of psoriasis, and the relationship between serum leptin levels and the severity of psoriasis in Chinese Han patients. We also investigated biological effects of leptin on the proliferation and secretion of pro‐inflammatory cytokines by human keratinocytes in vitro. Obesity was a significant risk factor for psoriasis in the Chinese Han population; however, we did not observe a significant correlation between Psoriasis Area and Severity Index (PASI) and body mass index (BMI). We observed a positive correlation between the serum leptin level and PASI in overweight and obese male patients with psoriasis. Strong leptin immunoreactivity was detected in the epidermis of psoriatic lesions, particularly in keratinocytes. Leptin significantly increased the proliferation and secretion of pro‐inflammatory cytokines by keratinocytes in vitro. In conclusion, this study suggests leptin as a novel molecular link between psoriasis and obesity, which may help to explain the more server conditions of psoriasis in patients with obesity.     

Prevention of Topical Surfactant–Induced Itch-Related Responses by Chlorogenic Acid Through the Inhibition of Increased Histamine Production in the Epidermis

Effects of chlorogenic acid on surfactant-induced itching were studied in mice. Topical application of sodium laurate increased hind-paw scratching, an itch-related response, 2 h after application, which was inhibited by topical post-treatment with chlorogenic acid. Sodium laurate increased the histamine content and 53-kDa l-histidine decarboxylase in the epidermis, which were also inhibited by post-treatment with chlorogenic acid. These results suggest that topical chlorogenic acid is effective in the prevention of itching induced by anionic surfactants. The inhibitory activity of chlorogenic acid may be due to the inhibition of an increase in histamine in the epidermis.     

Ultraviolet B radiation regulates cysteine‐rich protein 1 in human keratinocytes

Background: Cysteine‐rich protein 1 (CRP1) is a growth‐inhibitory cytoskeletal protein that is induced by ultraviolet (UV) C radiation radiation in fibroblasts. Our aim was to investigate the effects of UV radiation on CRP1 in keratinocytes, the main cell type subjected to UV radiation in the human body. Methods: The effects of physiologically relevant doses of UVB radiation on CRP1 protein levels were studied in cultured primary keratinocytes and transformed cell lines (HaCaT, A‐431) by immunoblotting. UVB‐induced keratinocyte apoptosis was assessed by flow cytometry and monitoring caspase activity. Expression of CRP1 in human skin in vivo was studied by immunohistochemistry in samples of normal skin, actinic keratosis (AK) representing UV‐damaged skin and squamous cell carcinoma (SCC), a UV‐induced skin cancer. Results: CRP1 expression increased by UVB radiation in primary but not in immortalized keratinocytes. Upon high, apoptosis‐inducing doses of UV radiation, CRP1 was cleaved in a caspase‐dependent manner. In normal skin, CRP1 was expressed in smooth muscle cells, vasculature, sweat glands, sebaceous glands and hair root sheath, but very little CRP1 was present in keratinocytes. CRP1 expression was elevated in basal cells in AK but not in SCC. Conclusion: CRP1 expression is regulated by UVB in human keratinocytes, suggesting a role for CRP1 in the phototoxic responses of human skin.     

Tissue factor antisense deoxyoligonucleotide prevents monocrotaline/LPS hepatotoxicity in mice

Tissue factor (TF) is a membranous glycoprotein that functions as a receptor for coagulation factor VII/VIIa and activates the coagulation system when blood vessels or tissues are damaged. TF was upregulated in our monocrotaline (MCT)/lipopolysaccharide (LPS) hepatotoxicity model. We tested the hypothesis that TF‐dependent fibrin deposition and lipid peroxidation in the form of oxidized low‐density‐lipoprotein (ox‐LDL) accumulation contribute to liver inflammation induced by MCT/LPS in mice. In the present study, we blocked TF using antisense oligodeoxynucleotides against mouse TF (TF‐ASO). TF‐ASO (5.6 mg kg^?1) was given i.v. to ND4 male mice 30 min after administration of MCT (200 mg kg^?1) p.o. followed after 3.5 h by LPS i.p. (6 mg kg^?1). Blood alanine aminotransferase (ALT), TF, ox‐LDL, platelets, hematocrit and keratinocyte‐derived chemokine (KC) levels were evaluated in different treatment groups. Fibrin deposition and ox‐LDL accumulation were also analyzed in the liver sections using immunofluorescent staining. The results showed that TF‐ASO significantly restored blood ALT, hematocrit and KC levels, distorted after MCT/LPS co‐treatment, as well as preventing the accumulation of ox‐LDL and the deposition of fibrin in the liver tissues, and thereby inhibited liver injury caused by MCT/LPS. In a separate experiment, TF‐ASO administration significantly prolonged animal survival. The current study demonstrates that TF is associated with MCT/LPS‐induced liver injury. Administration of TF‐ASO successfully prevented this type of liver injury. Copyright © 2012 John Wiley & Sons, Ltd.     

Heparanase activation induces epidermal hyperplasia,angiogenesis, lymphangiogenesis and wrinkles

Please cite this paper as: Heparanase activation induces epidermal hyperplasia, angiogenesis, lymphangiogenesis and wrinkles. Experimental Dermatology 2010; 19 : 965–972. Abstract: To clarify the difference between cutaneous responses to single and repeated barrier disruption, changes of epidermal gene expression were examined by using RT‐PCR. In repeatedly barrier‐disrupted skin, heparanase was specifically up‐regulated in epidermis. In addition, there was a marked decrease in heparan sulfate (HS) chains of perlecan in basement membrane at the dermal–epidermal junction (DEJ) compared with singly disrupted skin. HS chains form a reservoir for heparan sulfate‐binding growth factors. In repeatedly barrier‐disrupted skin, expression of vascular endothelial growth factor‐A (VEGF‐A), an angiogenic factor, was induced in epidermis, whereas thrombospondin‐1 (TSP‐1), an angiogenesis inhibitor, was down‐regulated, and concomitantly blood vessels were elongated and enlarged in dermis. Expression of VEGF‐C, a lymphangiogenesis factor, was augmented in epidermis of repeatedly barrier‐disrupted skin, concomitantly with an increase in the number and size of lymphatic vessels. Topical application of a synthetic heparanase inhibitor, 1‐[4‐(1H‐benzoimidazol‐2‐yl)phenyl]‐3‐[4‐(1H‐benzoimidazol‐2‐yl)phenyl]urea, to skin after barrier disruption significantly suppressed wrinkle formation, degradation of HS chains in the basement membrane, epidermal hyperplasia and the changes of blood and lymphatic vessels. These results suggest that chronic barrier disruption activates heparanase and induces gene expression changes, leading to increased growth factor interaction between epidermis and dermis, and facilitating various cutaneous changes, including wrinkle formation.