ABSTRACT
Background@#Local hyperthermia is recommended for the treatment of patients with fixed cutaneous sporotrichosis, though the effectiveness and mechanisms of action remain elusive. While neutrophils represent the main inflammatory cells associated with sporotrichosis lesions, the issue of whether hyperthermia is involved with interactions between neutrophils and Sporothrix globosa remains unclear. @*Objective@#To evaluate the effect of local hyperthermia on sporotrichosis and determine whether local hyperthermia involves effects of neutrophils against Sporothrix. @*Methods@#For the in vivo study, mice were infected with yeast cells of S. globosa followed by treatment with local hyperthermia. In vitro, an isolated S. globosa strain was co-cultured with or without neutrophils and subjected under different temperatures. Immunofluorescence was used to assess the formation of neutrophil extracellular trap (NETs) were formed under these different culture conditions and the number of fungi colony forming units were compared. Results: Hyperthermia was significantly more effective in clearing the lesions in the mouse model, as compared to sham treatment. Neutrophils failed to exert any fungicidal effects against S. globosa in response to hyperthermia. Moreover, NETs were formed after interactionwith S. globosa, and the percentage of NETs formed was not significantly different at 41o C or 37o C. @*Conclusion@#While hyperthermia could serve as an effective therapy for fixed cutaneous sporotrichosis, this ability does not involve the formation of NETs.
ABSTRACT
BACKGROUND@#As a potent pro-inflammatory cytokine of the interleukin (IL)-1 family, IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index (PASI). Although results from previous studies have established that IL-18 may aggravate psoriatic inflammation, the mechanisms of this process remain unknown. In this study, IL-18 knock out (KO) mice and wild-type (WT) mice were used to investigate the effects of IL-18 within a mouse model of psoriasis.@*METHODS@#WT and IL-18 KO mice were divided into four groups, including imiquimod (IMQ)-treated IL-18 KO group (n = 11) and WT group (n = 13) as well as their respectively gene-matched control mice (receiving vaseline; n = 12). PASI scores were used to evaluate psoriatic lesions in IMQ-treated mice. Pathological features and dermal cellular infiltration were investigated by hematoxylin and eosin staining. The levels of psoriasis-related cytokines including IL-23, IL-17, IL-12, IL-1β, IFNγ, IL-15, IL-27, and IL-4 were tested by real-time polymerase chain reaction (PCR). The protein level of IL-1β, IL-27, CXCL1, and Ly6 g were investigated by immunohistochemistry (IHC).@*RESULTS@#Acanthosis (98.46 ± 14.12 vs. 222.68 ± 71.10 μm, P < 0.01) and dermal cell infiltration (572.25 ± 47.45 vs. 762.47 ± 59.59 cells/field, P < 0.01) were significantly milder in IMQ-induced IL-18 KO mice compared with that in WT mice. IMQ-induced IL-18 KO mice manifested larger areas of Munro microabscesses (11,467.83 ± 5112.09 vs. 4093.19 ± 2591.88 μm, P < 0.01) and scales (100,935.24 ± 41,167.77 vs. 41,604.41 ± 14,184.10 μm, P < 0.01) as compared with WT mice. In skin lesions of IL-18 KO mice, the expressions of IL-1β, IL-4, and IL-27 were all significantly upregulated but IL-17 was decreased. Histologically, strong positive signals of Ly6g were observed within the epidermis of IL-18 KO mice but expressions of CXCL1 were decreased.@*CONCLUSIONS@#IL-18 may exacerbate prominent inflammation and influence pathological features in IMQ-induced mouse model of psoriasis. IL-18 may upregulate pro-inflammatory cytokines and reduce protective cytokines, thus aggravating psoriatic inflammation. In addition, IL-18 may be involved in the formation of Munro microabscesses and scales.
Subject(s)
Animals , Mice , Chemokine CXCL1 , Metabolism , Cytokines , Metabolism , Disease Models, Animal , Imiquimod , Toxicity , Interleukin-17 , Metabolism , Interleukin-18 , Metabolism , Mice, Knockout , Psoriasis , Genetics , Metabolism , Skin , Allergy and Immunology , MetabolismABSTRACT
<p><b>BACKGROUND</b>Seborrheic dermatitis (SD) is a common inflammatory skin condition. The etiology is unclear, although overgrowth of Malassezia on the skin has been suggested to cause SD. This study investigated whether colonization with Staphylococcus plays a role in facial SD, which was not well addressed previously.</p><p><b>METHODS</b>The study was conducted from September 1, 2011 to February 20, 2012 in the First Hospital of China Medical University. In the first phase, the study evaluated the level of transepidermal water loss (TEWL) and the number of colony-forming units (CFU) of Staphylococcus in defined skin areas of SD patients who were human immunodeficiency virus (HIV) seropositive (HIV [+] SD [+] group, n = 13), classical SD (HIV [-] SD [+] group, n = 24) patients, HIV seropositive-non-SD (HIV [+] SD [-] group, n = 16) patients, and healthy volunteers (HIV [-] SD [-] group, n = 16). In the second phase, we enrolled another cohort of HIV (-) SD (+) patients who applied topical fusidic acid (n = 15), tacrolimus (n = 16), or moisturizer (n = 12). Changes in the Seborrheic Dermatitis Area Severity Index (SDASI), TEWL, and Staphylococcus density were evaluated 2 weeks later. Comparisons of each index were performed using analysis of variance (ANOVA) and least significant difference method.</p><p><b>RESULTS</b>The level of TEWL was greater through lesional sites in the HIV (+) SD (+) group than that in HIV (+) SD (-) and HIV (-) SD (-) groups (95% confidence interval [CI]: 18.873-47.071, P < 0.001 and 95% CI: 28.755-55.936, P < 0.001, respectively). The number of CFU of Staphylococcus was greater in the HIV (+) SD (+) group than that in HIV (+) SD (-) and HIV (-) SD (-) groups (95% CI: 37.487-142.744, P = 0.001 and 95% CI: 54.936-156.400, P < 0.001, respectively). TEWL was significantly more improved in patients treated with tacrolimus and fusidic acid than that in those treated with moisturizers (95% CI: 7.560-38.987, P = 0.004 and 95% CI: 4.659-37.619, P = 0.011, respectively). Topical tacrolimus and fusidic acid were significantly associated with decreased SDASI as compared with moisturizer (95% CI: 0.03-0.432, P = 0.025 and 95% CI: 0.033-0.44, P = 0.024, respectively).</p><p><b>CONCLUSIONS</b>High colonization with Staphylococcus epidermidis, along with impaired skin permeability barrier function, contributes to the occurrence of SD.</p>
ABSTRACT
<p><b>BACKGROUND</b>Atopic dermatitis (AD) is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 (Th1/Th2) cytokine expression. Filaggrin (FLG) is the key protein to maintaining skin barrier function. Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes. However, the role of Th1/Th2 cytokines on FLG processing is not substantially documented. Our aim was to investigate the impact of Th1/Th2 cytokines on FLG processing.</p><p><b>METHODS</b>HaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin (IL)-4, 13 or interferon-γ (IFN-γ). FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) were measured by both real-time quantitative polymerase chain reaction and Western blotting. Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry.</p><p><b>RESULTS</b>IL-4/13 significantly reduced, while IFN-γ significantly up-regulated FLG expression. IL-4/13 significantly increased, whereas IFN-γ significantly decreased the expression of kallikreins 5 and 7, matriptase and channel-activating serine protease 1. On the contrary, IL-4/13 significantly decreased, while IFN-γ increased the expression of LEKTI and caspase-14. Similar trends were observed in AD lesions.</p><p><b>CONCLUSIONS</b>Our results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes. The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes.</p>