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Cutaneous Inflammation (cutaneous + inflammation)
Selected AbstractsInterleukin-6 cytokine family member oncostatin M is a hair-follicle-expressed factor with hair growth inhibitory propertiesEXPERIMENTAL DERMATOLOGY, Issue 1 2008Mei Yu Abstract:, The activation of receptor complexes containing glycoprotein 130 (gp130) identifies the interleukin (IL)-6 cytokine family. We examined members of this family for their expression and activity in hair follicles. Quantitative polymerase chain reaction using mRNA derived from microdissected, anagen-stage human hair follicles and comparison to non-follicular skin epithelium revealed higher levels of IL-6 (15.5-fold) and oncostatin M (OSM, 3.4-fold) in hair follicles. In contrast, expression of all mRNAs coding for IL-6 cytokine family receptors was reduced. Immunohistology suggested expression of OSM, gp130, leukaemia inhibitory factor receptor (LIFr) and IL-11r in the hair follicle root sheaths and dermal papilla, while IL-11, IL-6r and OSMr were expressed in root sheaths alone. IL-6 was expressed in the dermal papilla while cardiotrophin-1 (CT-1) and LIF were not observed. OSM and to a lesser extent CT-1 exhibited a dose-dependent growth inhibition capacity on human hair follicles in vitro. OSM and CT-1 incubated with agarose beads and injected subcutaneously at 1 ,g per mouse into telogen skin of 65-day-old mice revealed no capacity to induce anagen hair growth. In contrast, injection of 65-day-old mice in which anagen had been induced by hair plucking revealed a moderate hair growth inhibitory capacity for OSM, but no significant effect for CT-1. The data identify OSM as a modulator of hair follicle growth and suggest other family members may also have some degree of hair growth inhibitory effect. In principle, increased expression of some IL-6 cytokine family members in cutaneous inflammation might contribute to the promotion of hair loss. [source] Anti-inflammatory effects in the skin of thymosin-,4 splice-variantsIMMUNOLOGY, Issue 1 2003Michael Girardi Summary The intraepithelial lymphocyte (IEL) network of T-cell receptor ,,+ (V,5+) dendritic epidermal T cells (DETC) in murine skin down-regulates cutaneous inflammation, although the mechanism is unknown. Thymosin-,4 (T,4), identified by serial analysis of gene expression as a predominant transcript in gut IEL, encodes both a ubiquitous actin-binding protein (UT,4) with demonstrated capacity to inhibit neutrophilic infiltration, and a splice-variant limited to lymphoid tissue (LT,4) with unknown bioactivity. Freshly isolated V,5+ DETCs expressed both forms, while only LT,4 was preferentially up-regulated after cellular activation in vitro. To compare the anti-inflammatory properties of LT,4 and UT,4 in the skin in vivo, the biological activities of synthesized polypeptides were assessed using three different strategies: neutrophil infiltration by footpad ,-carrageenan injection; irritant contact dermatitis to 12-O-tetradecanoylphorbol 13-acetate; and allergic contact dermatitis to 2,4-dinitrofluorobenzene. These studies clearly showed that the anti-inflammatory activities of LT,4 were broader and most often stronger than those of UT,4. Thus, the activation-responsive expression of the lymph-specific form of T,4 may be one mechanism by which DETC, and possibly other IELs, down-regulate local inflammation. [source] Two modes of ERK activation by TNF in keratinocytes: Different cellular outcomes and bi-directional modulation by vitamin D,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2008Ester Ziv Abstract Inflammation, elicited in the skin following tissue damage or pathogen invasion, may become chronic with deleterious consequences. Tumor necrosis factor (TNF) is a key mediator of cutaneous inflammation and the keratinocyte an important protagonist of skin immunity. Calcitriol, the hormonally active vitamin D metabolite, and its analogs attenuate epidermal inflammation and inhibit the hyperproliferation of keratinocytes associated with the inflammatory disorder, psoriasis. Since activation of extracellular signal-regulated kinase (ERK) promotes keratinocyte proliferation and mediates epidermal inflammation, we studied the effect of calcitriol on ERK activation in HaCaT keratinocytes exposed to the ubiquitous inflammatory cytokine TNF. By using the EGF receptor (EGFR) tyrosine kinase inhibitor, AG1487 and the Src family inhibitor, PP-1, we established that TNF activated ERK in an EGFR and Src dependent and an EGFR and Src independent modes. EGFR dependent activation resulted in the upregulation of the transcription factor, c-Fos, while the EGFR independent activation mode was of a shorter duration, did not affect c-Fos expression but induced IL-8 mRNA expression. Pretreatment with calcitriol, enhanced TNF-induced EGFR-Src dependent ERK activation and tyrosine phosphorylation of the EGFR, but abolished the EGFR-Src independent ERK activation. These effects were mirrored by enhancement of c-Fos and inhibition of IL-8 induction by TNF. Treatment with calcitriol increased the rate of the de-phosphorylation of activated ERK, accounting for the inhibition of EGFR-Src independent ERK activation by TNF. It is possible that effects on the ERK cascade contribute to the effects of calcitriol and its synthetic analogs on cutaneous inflammation and keratinocyte proliferation. J. Cell. Biochem. 104: 606,619, 2008. © 2007 Wiley-Liss, Inc. [source] Atopic xerosis: employment of noninvasive biophysical instrumentation for the functional analyses of the mildly abnormal stratum corneum and for the efficacy assessment of skin care productsJOURNAL OF COSMETIC DERMATOLOGY, Issue 2 2006Hachiro Tagami MD Summary The subtle dryness of the skin surrounding the lesions of atopic dermatitis (AD) is called atopic dry skin or atopic xerosis (AX). AX is more susceptible to the development of AD skin lesions under various environmental stimuli than the clinically normal skin of the people who have or have had or will have AD, which might be called normal atopic skin (NAS) that shows no functional differences as compared to the skin of normal individuals. Routine histopathologic studies of AX that involve the invasive procedures of biopsy are not so helpful in clarifying the underlying pathogenesis. Modern, noninvasive biophysical instrumentation provides rich and quantitative information about various functional aspects of skin. The stratum corneum (SC) of AX reveals not only decreased hydration but also mildly impaired barrier function demonstrable as an increase in transepidermal water loss, elevated pH values, and an increased turnover rate of the SC consisting of thick layers of smaller-sized corneocytes. These data suggest that AX is related to mildly increased epidermal proliferation as a result of the presence of subclinical cutaneous inflammation. Although AX skin does not display any impairment in the recovery of barrier function after physical skin irritation by tape-stripping, it produces a much more severe, long-lasting inflammatory response together with a delay in barrier repair after chemical irritation such as that induced by sodium lauryl sulphate. The SC of AX is biochemically characterized by reduction in the amounts of ceramides, especially ceramide I, sebum lipids, and water-soluble amino acids. None of these changes in SC functions are seen in NAS, which includes not only the normal-looking skin of AD patients long after regression of all active lesions but also of latent atopic skin such as neonates who later develop AD. This suggests that all of the observed functional as well as biochemical abnormalities of AX are a reflection of subclinical inflammation. The presence of the underlying inflammation in AX also differentiates it from senile xerosis. The mildly impaired SC functions of AX can be improved by daily repeated applications of effective moisturizers, i.e., corneotherapy, which is effective in preventing the exacerbating progression of AX to AD resulting from inadvertent scratching of the skin that facilitates the penetration of environmental allergens into the skin. The biophysical confirmation of such efficacy of moisturizers, including cosmetic bases on the mildly impaired barrier function and decreased water-holding capacity of the SC of AX, definitely substantiates the importance of skin care for the cosmetic skin problems that affect every individual in the cold and dry season ranging from late autumn to early spring. [source] Interleukin (IL)-31 induces pro-inflammatory cytokines in human monocytes and macrophages following stimulation with staphylococcal exotoxinsALLERGY, Issue 6 2010S. Kasraie To cite this article: Kasraie S, Niebuhr M, Werfel T. Interleukin (IL)-31 induces pro-inflammatory cytokines in human monocytes and macrophages following stimulation with staphylococcal exotoxins. Allergy 2010; 65: 712,721. Abstract Background:, IL-31 is a cytokine expressed by T cells following activation with cytokines or staphylococcal exotoxins. A major function of IL-31 in atopic dermatitis (AD) is the induction of pruritus in the skin via the IL-31 receptor on sensory nerve cells. However, the regulation of the IL-31 receptor and pro-inflammatory functions of IL-31 in human monocytes and monocyte-derived cells are yet to be studied in detail. Objective: To investigate the regulation and function of IL-31 receptors in resting and activated human monocytes, macrophages and dendritic cells. Methods:, Human monocytes, macrophages and dendritic cells were stimulated with staphylococcal exotoxins (SEB, ,-toxin) or cytokines (IFN-,, IL-13). IL-31RA expression and regulation were then investigated at both the mRNA and the protein level. Subsequently, functional effects of IL-31 stimulation on cytokine secretion were measured at the protein level. Results:, Staphylococcal exotoxins significantly up-regulated IL-31RA expression on monocytes and macrophages but not on dendritic cells at both the mRNA and the protein level. IL-31 enhanced the secretion of IL-1,, IL-6 and IL-18 and up-regulated CD86 expression. In patients with AD, functional IL-31RA was also detected following stimulation of PBMC with IFN-,. However, this was not observed in healthy individuals. Conclusion:, IL-31 induces pro-inflammatory effects in activated human monocytes and macrophages. This may have implications for cutaneous inflammation in eczema where an over-expression of IL-31 has been described previously. Moreover, our findings provide a new link between staphylococcal colonization and the worsening of inflammation via IL-31. Further therapeutic considerations may include IL-31 as a target in AD. [source] The immunology of susceptibility and resistance to scabiesPARASITE IMMUNOLOGY, Issue 8 2010S. F. WALTON Summary The transmission of scabies occurs with the burrowing of Sarcoptes scabiei var. hominis mites into the skin. Infestation invariably leads to the development of localized cutaneous inflammation, pruritis and skin lesions. Classical transmission studies document an initial increase in S. scabiei numbers subsequent to primary infestation with a gradual reduction as host immunity develops. However, certain individuals fail to control infection and develop severe crusting of the skin, accompanied with extremely high mite burdens, elevated antibody levels and eosinophilia. These individuals have the nonhealing form of the human disease known as crusted scabies. The genetic predisposition for susceptibility or resistance to S. scabiei infection in humans is hypothesized to correlate with the dominance of an IgE-driven Th2 response in severe disease or an interferon-,-dominated Th1 response that promotes parasite control. However, recent data reveals complexities in cytokine regulation in the skin and the mechanisms of acquired resistance and immune escape. In this review, we consider the recent immunological and biomolecular advances in understanding the human host immune response to S. scabiei infestations in the context of earlier studies and attempt to reconcile apparent differences and emphasize those aspects of the Th1/Th2 model that are supported or refined. [source] Adaptation of the Human Skin by Chronic Solar-simulating UV Irradiation Prevents Ultraviolet-B Irradiation-induced Rise in Serum C-Reactive Protein Levels,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2005Jarmo K. Laihia ABSTRACT Exposure of the skin to UV radiation induces local inflammation. We hypothesized that inflammation induced by erythemal UV-B irradiation could elevate levels of serum C-reactive protein (CRP) and that suberythemal repeating doses of solar-simulating UV radiation (SSR) would produce photoadaptation to such inflammation. Separation-free high-sensitivity assays of CRP show an increase by 42% (P= 0.046) in CRP concentrations in healthy human subjects 24 h after a 3 minimal erythemal dose (MED) dose of UV-B delivered onto a 100 cm2 skin area. Preceding daily suberythemal doses of whole-body SSR for 10 or 30 consecutive days completely prevented the CRP increase. UV-B-induced skin erythema was partially attenuated by 30 preceding days of SSR only (P= 0.00066). After 10 daily SSR doses, the mean baseline CRP concentrations (0.24 ± 0.21 mg/L) declined by 35% (P= 0.018). Using high-sensitivity analysis of serum CRP as the endpoint marker for cutaneous inflammation, we show that acute exposure of even a relatively small skin area to erythemal UV-B induces skin inflammation detectable also at the systemic level and that photoadaptation by preceding repeating suberythemal doses of SSR reduces signs of inflammation. Our data complement the view given by previous studies in that local photoadaptation also has systemic manifestations. [source] Secondary cutaneous candidiasis with eosinophiliaTHE JOURNAL OF DERMATOLOGY, Issue 2 2010Yuichiro TSUNEMI Abstract Cutaneous candidiasis is a common skin infection caused by the Candida species, especially in intertriginous areas, and neutrophils usually infiltrate histopathologically. We describe a case of secondary cutaneous candidiasis which spread extensively to the trunk and extremities and showed marked dermal eosinophilia. This case and a similar reported case suggest that Candida can sometimes cause cutaneous inflammation predominantly composed of eosinophils. [source] Neutrophil dysfunction in a family with a SAPHO syndrome,like phenotypeARTHRITIS & RHEUMATISM, Issue 10 2008Polly J. Ferguson SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) is an inflammatory disorder of the bone, skin, and joints. We describe a family with multiple affected members who segregate a SAPHO syndrome,like phenotype, and we report the results of neutrophil studies and candidate gene analysis. We obtained written informed consent and a family history and reviewed medical records. We collected DNA and sequenced candidate genes, and we performed functional studies on neutrophils isolated from the proband and her mother. The pedigree segregated chronic osteomyelitis and cutaneous inflammation in a pattern that suggested an autosomal-dominant disorder. No coding sequence mutations were detected in PSTPIP1,PSTPIP2, LPIN2, SH3BP2, or NCF4. Analysis of neutrophil function in the proband, including nitroblue tetrazolium tests, myeloperoxidase assays, neutrophil chemotaxis, and neutrophil chemotaxis assays, revealed no identifiable abnormalities. However, an abnormality in the luminol, but not the isoluminol, respiratory burst assays following stimulation with phorbol myristate acetate (PMA) was detected in neutrophils isolated from the affected proband. Internal oxidant production was also reduced in the proband and her mother when neutrophils were treated with fMLP with or without platelet-activating factor, PMA alone, or tumor necrosis factor , alone. This family segregates a disorder characterized by chronic inflammation of the skin and bone. Functional differences in neutrophils exist between affected individuals and controls. The biologic significance of this defect remains unknown. Identification of the gene defect will help identify an immunologic pathway that, when dysregulated, causes inflammation of the skin and bone. [source] Recombinant, ETA,-based CD64 immunotoxins: improved efficacy by increased valency, both in vitro and in vivo in a chronic cutaneous inflammation model in human CD64 transgenic miceBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2010T. Ribbert Summary Background, Dysregulated, activated macrophages play a pivotal role in chronic inflammatory diseases such as arthritis and atopic dermatitis. These cells display increased expression of the high-affinity Fc, receptor (CD64), making them ideal targets for CD64-specific immunotoxins. We previously showed that a chemically linked immunotoxin, the monoclonal H22-RicinA, specifically eliminated infiltrating activated macrophages and resolved chronic cutaneous inflammation. However, several disadvantages are associated with classic immunotoxins, and we therefore followed a fusion protein strategy to express the antigen-binding site alone (scFv H22) fused to a derivative of Pseudomonas exotoxin A (ETA,). Objectives, To assess the potential effect of increased valency on efficacy, we produced monovalent [H22(scFv)-ETA,] and bivalent [H22(scFv)2 -ETA,] versions and evaluated their potential for eliminating activated macrophages both in vitro and in vivo. Methods, Both immunotoxins were produced by bacterial fermentation. Binding was assessed by flow cytometry on the monocytic CD64+ cell line U937. Toxicity was analysed by XTT and apoptosis induction by annexin V bioassay. The in vivo effect was tested in a human CD64 transgenic mouse model for cutaneous inflammation. Results, The cytotoxic effects of both immunotoxins were clearly due to apoptosis with an IC50 of 140 pmol L,1 for monovalent and only 14 pmol L,1 for the divalent version. In vivo treatment with H22(scFv)-ETA, reduced CD64+ activated macrophages to 21% of their initial numbers whereas H22(scFv)2 -ETA, treatment reduced these cells to 4·8% (P < 0·001). Conclusions, These data clearly show increased efficacy due to increased valency of the anti-CD64 immunotoxin. Both recombinant immunotoxins have a low IC50, making them suitable for the treatment of diseases involving dysregulated, activated macrophages. [source] Topical treatment of perianal eczema with tacrolimus 0·1%BRITISH JOURNAL OF DERMATOLOGY, Issue 6 2009J. Schauber Summary Background, Perianal eczema is an inflammatory skin disease with a high prevalence in most industrialized countries. As general practitioners and dermatologists frequently see patients with perianal eczema the need for efficient, fast and safe therapies is high. Topical calcineurin inhibitors such as tacrolimus (FK506) ameliorate cutaneous inflammation and associated pruritus in an array of inflammatory dermatoses. Objectives, To investigate the effect of topical tacrolimus in perianal eczema. Methods, Twenty-four patients with perianal eczema were treated with tacrolimus 0·1% ointment twice daily on the affected skin area for 2 weeks. Results, All returning patients showed clinical improvement as assessed by macroscopic appearance and clinical score (modified SCORAD index). Conclusions, In this short-term trial we demonstrate that topical tacrolimus 0·1% is safe, efficient and well tolerated in patients with perianal eczema irrespective of the underlying cause. [source] A role for T cell-derived interleukin 22 in psoriatic skin inflammationCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007K. Boniface Summary Interleukin (IL)-22 is a T cell-derived cytokine that has been reported recently to induce cutaneous inflammation in an experimental murine model of psoriasis, and to induce in vitro an inflammatory-like phenotype. In the present study, we assessed the presence of IL-22 and the IL-22 receptor 1 (IL-22R1) in skin lesions, skin-derived T cells, as well as IL-22 levels in sera from patients with psoriasis. IL-22R1 and IL-10R2 transcripts are expressed at a similar level in psoriatic and healthy skin. In contrast, IL-22 mRNA expression was up-regulated in psoriatic skin lesions compared to normal skin, whereas IL-22 mRNA levels in peripheral blood mononuclear cells from psoriatic patients and normal subjects were similar. Circulating IL-22 levels were significantly higher in psoriatic patients than in normal subjects. T cells isolated from psoriatic skin produced higher levels of IL-22 in comparison to peripheral T cells isolated from the same patients. IL-10 was expressed at similar levels in skin biopsies and peripheral blood mononuclear cells of psoriatic patients and normal subjects. Finally, we show here that supernatants of lesional psoriatic skin-infiltrating T cells induce an inflammatory response by normal human epidermal keratinocytes, resembling that observed in psoriatic lesions. Taken together, the results reported in this study indicate that IL-22 is a cytokine produced by skin-infiltrating lymphocytes that is potentially involved in initiation and/or maintenance of the pathogenesis of psoriasis. [source] | |||||||||||||||||||||||||