Chemokine receptor CX3CR1 promotes local remodeling of monocyte-derived Langerhans cell subsets to maintain chronic skin inflammation / 中华微生物学和免疫学杂志

Objective:To investigate the role of chemokine receptor CX3CR1 in chronic skin inflammation and its regulatory mechanism.Methods:Wild type (WT) C57BL/6 mice and Cx3 cr1 GFP/GFP mice were induced by DNFB to establish acute and chronic allergic contact dermatitis (ACD) model. Ear inflammation and swelling were observed with hematoxylin-eosin (HE) staining. Flow cytometry (FCM) was used to detect the changes in classical Langerhans cell (LC) and monocyte-derived LC (Mo-LC), as well as the expression of major histocompatibility complex Ⅱ (MHCⅡ), inducible nitric oxide synthase (iNOS) and TNF-α. Changes in epidermal LC in UV irradiation-induced dermatitis models were also analyzed. In human chronic skin inflammation, CX3CL1 expression was detected using immunohistochemistry, RT-PCR and Western blot and CD1a, CD14 and CD207 expression was observed with immunofluorescence staining. Results:In the chronic ACD model, Cx3 cr1 GFP/GFP mice showed significantly alleviated ear inflammatory and swelling as compared with WT mice, but no significant difference was found in the acute ACD model. The percentages of Mo-LC were decreased in the chronic ACD model and after three weeks of UV irradiation. Moreover, MHCⅡ, TNF-α and iNOS expressed by Mo-LC were significantly upregulated as compared with those by classical LC. CX3CL1 expression was significantly upregulated and the numbers of CD14 + monocytes and CD1a + langerin - Mo-LC were dramatically increased in human chronic skin inflammation. Conclusions:CX3CR1 might maintain inflammatory response by regulating local remodeling of Mo-LC in chronic skin inflammation.

CORM-2-entrapped ultradeformable liposomes ameliorate acute skin inflammation in an ear edema model

The short release half-life of carbon monoxide (CO) is a major obstacle to the effective therapeutic use of carbon monoxide-releasing molecule-2 (CORM-2). The potential of CORM-2-entrapped ultradeformable liposomes (CORM-2-UDLs) to enhance the release half-life of CO and alleviate skin inflammation was investigated in the present study. CORM-2-UDLs were prepared by using soy phosphatidylcholine to form lipid bilayers and Tween 80 as an edge activator. The deformability of CORM-2-UDLs was measured and compared with that of conventional liposomes by passing formulations through a filter device at a constant pressure. The release profile of CO from CORM-2-UDLs was evaluated by myoglobin assay.

TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization

Cutaneous neurogenic inflammation (CNI) is inflammation that is induced (or enhanced) in the skin by the release of neuropeptides from sensory nerve endings. Clinical manifestations are mainly sensory and vascular disorders such as pruritus and erythema. Transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively) are non-selective cation channels known to specifically participate in pain and CNI. Both TRPV1 and TRPA1 are co-expressed in a large subset of sensory nerves, where they integrate numerous noxious stimuli. It is now clear that the expression of both channels also extends far beyond the sensory nerves in the skin, occuring also in keratinocytes, mast cells, dendritic cells, and endothelial cells. In these non-neuronal cells, TRPV1 and TRPA1 also act as nociceptive sensors and potentiate the inflammatory process. This review discusses the role of TRPV1 and TRPA1 in the modulation of inflammatory genes that leads to or maintains CNI in sensory neurons and non-neuronal skin cells. In addition, this review provides a summary of current research on the intracellular sensitization pathways of both TRP channels by other endogenous inflammatory mediators that promote the self-maintenance of CNI.

Therapeutic effect of ethyl acetate extract from Asparagus cochinchinensis on phthalic anhydride-induced skin inflammation / 한국실험동물학회지

Asparagus cochinchinensis has been used to treat various diseases including fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease, while IL-4 cytokine has been considered as key regulator on the skin homeostasis and the predisposition toward allergic skin inflammation. However, few studies have investigated its effects and IL-4 correlation on skin inflammation to date. To quantitatively evaluate the suppressive effects of ethyl acetate extracts of A. cochinchinensis (EaEAC) on phthalic anhydride (PA)-induced skin inflammation and investigate the role of IL-4 during their action mechanism, alterations in general phenotype biomarkers and luciferase-derived signals were measured in IL-4/Luc/CNS-1 transgenic (Tg) mice with PA-induced skin inflammation after treatment with EaEAC for 2 weeks. Key phenotype markers including lymph node weight, immunoglobulin E (IgE) concentration, epidermis thickness and number of infiltrated mast cells were significantly decreased in the PA+EaEAC treated group compared with the PA+Vehicle treated group. In addition, expression of IL-1β and TNF-α was also decreased in the PA+EaEAC cotreated group, compared to PA+Vehicle treated group. Furthermore, a significant decrease in the luciferase signal derived from IL-4 promoter was detected in the abdominal region, submandibular lymph node and mesenteric lymph node of the PA+EaEAC treated group, compared to PA+Vehicle treated group. Taken together, these results suggest that EaEAC treatment could successfully improve PA-induced skin inflammation of IL-4/Luc/CNS-1 Tg mice, and that IL-4 cytokine plays a key role in the therapeutic process of EaEAC.

Effect of Spa Spring Water on Cytokine Expression in Human Keratinocyte HaCaT Cells and on Differentiation of CD4+ T Cells

BACKGROUND: Skin acts as the first line of defense against any foreign materials outside of our body. In inflammatory skin disease, the pathogenesis is due to an immune reaction in the keratinocytes, immune cells and soluble mediators. Balneotherapy is widely used for the treatment of inflammatory skin disease, but the mechanisms are only partly understood by immune regulation. Balneotherapy in dermatologic disease can affect the secretion of pro-inflammatory cytokines, IL-1alpha and tumor necrosis factor from keratinocytes, and possibly affect the T cell differentiation. OBJECTIVE: In this study, we evaluated the effect of spa spring water from Yong-gung oncheon on the cells, and investigated the skin immune reaction. METHODS: We investigated the immunomodulatory or anti-inflammatory effect of thermal spring water on the expression of pro-inflammatory cytokines in the HaCaT cells under Toll-like receptor (TLR) stimulation, as well as the effect on the differentiation of CD4+ T cells under spring water. RESULTS: The treatment of spa spring water from Yong-gung oncheon decreased the expression of proinflammatory cytokines under TLR stimulation to the HaCaT cells and antigen presenting cells. In addition, spa spring water attenuated the differentiation process of subsets of CD4+ T cells, i.e., Th1, Th2 and Th17 cells. All these immune parameters can be used to evaluate the efficacy of spa spring water in Korea, in terms of the immune modulatory effect. CONCLUSION: Spa spring water treatment suppressed the inflammatory cytokines production and also modulated the differentiation of CD4+ T cells into Th1, Th2, and Th17 cells, but not the Tregs cells.

Effect of paeonol on the expression of MMP-9 mRNA and cytokines production in human skin fibroblasts induced by TNF-? / 中国药理学通报

Aim To explore the possible anti-inflammation mechanism of paeonol by investigating its effects on the MMP-9 mRNA expression and cytokines production in human dermal fibroblasts induced by TNF-?.Methods The effect of paneonol on the expression of MMP-9 mRNA was detected by semi-quantitative RT-PCR.The modulation of paneonol on the production of IL-1?,IL-6 and IL-8 in fibroblasts was measured by ELISA.Results MMP-9 hardly expressed in human dermal fibroblast.The results also showed that TNF-? significantly induced the expression of MMP-9 in fibroblasts and at the same time paeonol inhibited the expression of MMP-9.TNF-? stimulated the production of IL-1? and IL-8 in fibroblasts,while 10~100 mg?L-1 paeonol inhibited TNF-?-induced IL-1? and IL-8 production in fibroblasts but had nothing to do with the production of IL-6.Conclusions Paeonol can inhibit the expression of MMP-9 mRNA,IL-1? and IL-8 induced by TNF-?.

Expression and regulation characteristics of the Substance P receptor in human skin keratinocytes and Fibroblasts / 中国药理学通报

Aim To investigate the expression and regulation characteristics of the Substance P receptor(Neurokinin-1R, NK-1R) in human skin keratinocytes and fibroblasts. Methods HaCaT cells,a human keratinocyte cell line, and fibroblasts were cultured. The expression of NK-1R protein was examined by immunohistochemisury technique,and the mRNA level was detected by reverse transcriptase polymerase chain reaction (RT- PCR). The expression and regulation of NK-1R were measured by flow cytometry in HaCaT cells and fibroblasts treated with various stimuli and drugs. Results The expression of NK-1R existed in human keratinocyte and fibroblast, mainly located on cell membranes and cytoplasma. The NK-1R also expressed at HaCaT cells and fibroblasts transcription levels, and the mRNA levels in HaCaT cells were higher than that of fibroblasts. SP and IFN-? might upregulate the membrane expressions of NK-1R in both the two cells, while LPS might downregulate the expressions of NK-1R. Cetirizine and Spantide I can degrade the expressions of NK-1R in the two kinds of cells.Conclusions The human keratinocytes and fibroblasts can express NK- 1R at cell, protein and transcription levels, and the expression characteristics can be regulated by some inflammatory factors, it indicates the keratinocytes and fibroblasts were involved in the regulation of skin immune and NK-1R may play an important role in skin inflammation.

Platelet-activating factor and its receptor related with skin inflammation / 第二军医大学学报

Platelet activating factor(PAF), a potent phospholipid mediator of inflammation, has diverse physiological actions and participates in many diseases in vivo . In recent years, it has been revealed that PAF system involve in the expression of keratinocytes function and reaction of skin inflammation. Therefore, PAF system was found closely associated with inflammatory skin disease. Keratinocytes could express functional PAF receptors (PAF R) and involve in the action of epidermis cytokine system. The interaction between PAF system and other inflammatory mediators can lead to skin inflammatory cascade.