RESUMEN
Topical traditional Chinese medicine- (TTCM-) related contact dermatitis is not uncommon but ignored. Patch and photopatch tests using 6 individual herbal ingredients and Bai-Zhi-Kao (BZK; ), a skin-lightening TTCM preparation, were conducted on 30 participants. Twenty-five subjects showed at least 1 positive reaction, including 6 (20.0%) participants who reacted to BZK. The majority reacted to Radix Ampelopsis japonica (Bai-Lian; ) (60.0%), whereas few reacted to Rhizoma Bletilla striata (Bai-Ji; ) (16.7%), Rhizoma Atractylodis macrocephalae (Bai-Zhu; ) (10.0%), Radix Angelicae dahuricae (Bai-Zhi; ) (3.3%), and Herba asari (Xi-Xin; ) (3.3%). In the photopatch test, 3 participants (10.0%) reacted positively to BZK and 10 to ≥1 constituent; however, all reacted to Radix Angelicae dahuricae (26.7%), Radix Ampelopsis japonica (13.3%), and Rhizoma Bletilla striata (3.3%). In contrast, no subjects showed positive reactions to Sclerotium Poria cocos (Bai-Fu-Ling; ). Thus, BZK and its constituents might present potential latent risk of contact dermatitis owing to the possible presence of Radix Ampelopsis japonica and Radix Angelicae dahuricae. Furthermore, TTCMs, particularly cosmetic products, must be used carefully, with ample warning of potential contact dermatitis risk.
RESUMEN
Cutaneous T cell lymphoma (CTCL) is a clonal epidermotropic malignancy of memory T cells primarily involving the skin. However, the mechanisms governing migration of CTCL cells have not been fully clarified. It has been shown that certain chemokine receptors are upregulated in CTCL cells, but it remains unanswered whether these chemokine receptors play a critical role in the migration dynamics of CTCL. Using cell lines originally derived from patients with different subtypes of CTCL, we have shown higher CCR4 expression in the line derived from the mycosis fungoides (MJ), compared with the line derived from Sezary syndrome (Hut78). In specific responses to CCL22 (a CCR4 ligand) treatments, MJ cells showed significant chemotactic migration, enhanced activation and adhesion of certain integrins (CD49d and CD29) in vitro, while the control cells (Hut78, CD4+CD45RO+ memory T cells, and Jurkat cells) did not. Furthermore, compared with Hut78 cells, MJ cells manifested significantly more transendothelial migration in responses to treatments with either CCL22 or conditioned medium from dendritic cells in vitro. These results provide further dynamic evidence, in line with the multistep cascade paradigm for leukocyte transendothelial migration, to support a critical role for CCR4 in CTCL migration.
Asunto(s)
Linfoma Cutáneo de Células T/metabolismo , Linfoma Cutáneo de Células T/patología , Receptores CCR4/metabolismo , Enfermedades de la Piel/metabolismo , Enfermedades de la Piel/patología , Adhesión Celular , Quimiocina CCL22/metabolismo , Quimiocinas/metabolismo , Quimiocinas CXC , Quimiotaxis , Células Dendríticas/metabolismo , Endosomas/metabolismo , Humanos , Integrina alfa4beta1/metabolismo , Ligandos , Micosis Fungoide/metabolismo , Unión Proteica , Transducción de Señal , Células Tumorales CultivadasRESUMEN
To address whether matrix metalloproteinase (MMP)-2 expression by mesenchymal fibroblasts may be differentially modulated by interactions with normal or malignant epidermal cells, we set up a fibroblast co-culture model separately with keratinocytes, basal cell carcinoma cells and melanoma cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) and gelatin zymography were used to detect and quantify the expression of MMP-2 by these different kinds of cells. In independent cultures, MMP-2 was highly expressed by fibroblasts and melanoma cells constitutively, but barely expressed by keratinocytes and basal cell carcinoma (BCC) cells. MMP-2 expression by fibroblasts was downregulated in co-cultures with keratinocytes or BCC cells, but not with melanoma cells. These results indicate that epidermal-mesenchymal interactions are important modulators for MMP-2 expression by cutaneous cells and suggest a host-defense mechanism against the tumor progression of BCC.
Asunto(s)
Carcinoma Basocelular/enzimología , Fibroblastos/fisiología , Queratinocitos/fisiología , Metaloproteinasa 2 de la Matriz/metabolismo , Melanoma/enzimología , Neoplasias Cutáneas/enzimología , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Técnicas de Cocultivo , HumanosRESUMEN
The anticonvulsant carbamazepine (CBZ) frequently causes cutaneous adverse drug reactions (cADRs), including maculopapular eruption (MPE), hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We reported that SJS/TEN caused by CBZ is strongly associated with the HLA-B*1502 gene in Han Chinese. Here, we extended our genetic study to different types of CBZ-cADRs (91 patients, including 60 patients with SJS/TEN, 13 patients with hypersensitivity syndrome and 18 with maculopapular exanthema versus 144 tolerant controls). We used MALDI-TOF mass spectrometry to screen the genetic association of 278 single nucleotide polymorphisms (SNPs), which cover the major histocompatibility complex (MHC) region, tumor necrosis factor-alpha, heat shock protein and CBZ-metabolic enzymes, including CYP3A4, 2B6, 2C8, 2C9, 1A2 and epoxide hydrolase 1. In addition, we genotyped 20 microsatellites in the MHC region and performed HLA-typing to construct the recombinant map. We narrowed the susceptibility locus for CBZ-SJS/TEN to within 86 kb flanking the HLA-B gene on the extended B*1502 haplotype, and confirmed the association of B*1502 with SJS/TEN [Pc=1.6x10, odds ratio (OR)=1357; 95% confidence interval (CI)=193.4-8838.3]. By contrast to CBZ-SJS/TEN, HLA-B*1502 association was not observed in the MPE or HSS groups: MPE was associated with SNPs in the HLA-E region and a nearby allele, HLA-A*3101 (Pc=2.2x10, OR=17.5; 95% CI=4.6-66.5), and HSS with SNPs in the motilin gene (Pc=0.0064, OR=7.11; 95% CI=3.1-16.5) located terminal to the MHC class II genes. No SNPs in genes involved in CBZ metabolism were associated with CBZ-induced cADRs. Our data suggest that HLA-B*1502 could contribute to the pathogenesis of CBZ-SJS/TEN, and that genetic susceptibility to CBZ-induced cADRs is phenotype-specific.
Asunto(s)
Anticonvulsivantes/efectos adversos , Carbamazepina/efectos adversos , Hipersensibilidad a las Drogas/genética , Predisposición Genética a la Enfermedad , Antígenos HLA-B/genética , Estudios de Casos y Controles , Exantema/patología , Haplotipos , Humanos , Síndrome de Stevens-Johnson/inducido químicamente , Síndrome de Stevens-Johnson/complicaciones , Síndrome de Stevens-Johnson/patología , Síndrome de Stevens-Johnson/fisiopatologíaRESUMEN
BACKGROUND: Dihydrodiol dehydrogenase (DDH) is a member of the aldo-keto reductases superfamily which may be involved in normal detoxification process of environmental mutagenic hazards like polycyclic aromatic hydrocarbons (PAH). Previous clinical studies have demonstrated the over-expression of DDH in various types of cancers, including cutaneous squamous cell carcinoma (SCC), and its correlation with tumor progression and grave prognosis. OBJECTIVE: To investigate possible mechanisms for DDH's correlation with tumor progression and unfavorable prognosis. METHODS: DDH expression in SCC A431 cell line was examined by quantitative real-time PCR and immunoblotting. RNA interference (RNAi) by transduction with retroviral vector containing DDH-targeting small interfering RNA was employed to inhibit DDH expression by A431 cells. With DDH expression inhibited or not, sensitivity of A431 cells to UVB-induced apoptosis and cytotoxicity of chemotherapeutic agent bleomycin were then examined and compared. RESULTS: DDH was found highly expressed by SCC A431 cells, which was barely detectable in other normal or malignant cutaneous cells, including keratinocytes, fibroblast, and basal cell carcinoma cell line. RNAi Inhibition of DDH expression in A431 cells led to increased sensitivity to UVB-induced apoptosis and cytotoxicity of bleomycin treatment. CONCLUSION: DDH may play important roles in tumor progression of SCC via induction of apoptosis- and drug-resistance.
Asunto(s)
Apoptosis , Carcinoma de Células Escamosas/tratamiento farmacológico , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Oxidorreductasas/biosíntesis , Bleomicina/farmacología , Carcinoma de Células Escamosas/enzimología , Caspasa 3 , Caspasas/metabolismo , Línea Celular , Línea Celular Tumoral , Progresión de la Enfermedad , Fibroblastos/metabolismo , Humanos , Etiquetado Corte-Fin in Situ , Queratinocitos/metabolismo , Modelos Estadísticos , Hidrocarburos Policíclicos Aromáticos/metabolismo , Pronóstico , Interferencia de ARN , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/enzimología , Sales de Tetrazolio/farmacología , Tiazoles/farmacología , Rayos Ultravioleta , Regulación hacia ArribaRESUMEN
A 15-year-old, unmarried female presented to our dermatology department for an intensely pruritic skin rash that had appeared abruptly 3 days earlier. She had a remarkable medical history for a case of allergic rhinitis and several attacks of asthma in her early childhood. The condition waxed and waned initially but had improved in recent years. Physical examination revealed several erythematous plaques, papules studded with scattered pustules having diameters less than 0.3 mm. Conspicuous scratch marks had caused erythematous wheal-like indurations also studded with pustules in a linear distribution across the waist, forearms (Fig. 1), and back (Fig. 2). Discrete papulopustules were present on the face, nape and neck. The patient was otherwise healthy. There were no other symptoms such as fever, malaise, weakness, or lymphadenopathy Laboratory results were normal for hepatic and renal functions, serum electrolytes, glucose, protein, erythrocyte sedimentation rate (8 mm/h), and C-reactive protein (0.355 mg/l). A human immunodeficiency virus (HIV) antibody screen test was negative. Serum was positive for herpes simplex virus (HSV)-1 and HSV-2 IgG (in low titers), but negative for HSV-1 and HSV-2 IgM. White blood cell count revealed leukocytosis (11.2 x 10(3)/l), with a differential count of 68% neutrophils, 27% lymphocytes, and 8% eosinophils. Serum IgA, IgG, and IgM were within normal limits, but the IgE level was elevated (677 mg/dl). Cultures from peripheral blood and pustules were negative. A Tzank smear performed on the pustules showed no multinucleated giant cells. Fungal testing of skin scrapings from the initial lesion site gave negative results. Routine stool tests, including common pathogen and parasite screens, were negative, and urinalysis results were unremarkable. A biopsy specimen obtained from a skin pustule showed subcorneal eosinophilic and neutrophilic pustules in the follicular infundibulum with marked spongiosis of the follicular epithelium. (Fig. 3). There was a moderately dense superficial and deep perivascular mixed inflammatory cell infiltrate comprising eosinophils, neutrophils and lymphocytes. Migration of eosinophils and neutrophils through the vessel wall with variable luminal intramural fibrin deposition, histologically indicative of vasculopathy, was seen. There was concomitant slight perivascular dermal necrosis. (Fig. 4). Based on the clinical presentation and light microscopic findings on biopsy, a diagnosis of eosinophilic pustular folliculitis with pathergy was made. Systemic prednisolone 30 mg in divided doses was given. After 1 week of systemic corticosteroid therapy, the patient's condition was significantly improved and the patient was subsequently discharged. Two months later she had a relapse, upon which corticosteroid therapy was commenced leading to lesional resolution. The foci of eosinophilic folliculitis healed with areas of hyperpigmentation with variable scarring.
Asunto(s)
Eosinofilia/patología , Foliculitis/patología , Adolescente , Femenino , HumanosRESUMEN
Skin-derived migratory dendritic cells (DC), in contrast to bone marrow-derived DC (BMDC), express CXCR5, respond to the chemokine CXC ligand 13 (CXCL13) in vitro, and are capable of migrating to B cell zones (BCZ) in lymph nodes (LN) in vivo. Herein, we analyzed the surface phenotype of skin-derived migratory DC and found that 15-35% of MHC class II(high) cells showed high levels of expression of CXCR5 but expressed low levels of DEC205, a suggested characteristic of dermal-type DC in mice. To study the effects of CXCR5 on the trafficking dynamics of DC, we stably expressed CXCR5 in BMDC by retroviral gene transduction. CXCR5 was detected by flow cytometry on transduced cells, which responded to CXCL13 in vitro in chemotaxis assays (3-fold over nontransduced BMDC, p < 0.01). When injected into the footpads of mice, approximately 40% of injected CXCR5-BMDC were observed in BCZ of draining LN. Mice were vaccinated with CXCR5- and vector-BMDC that were pulsed with keyhole limpet hemocyanin (KLH) to induce Ag-specific cellular and humoral immune responses. Mice injected with CXCR5-BMDC (vs vector-BMDC) demonstrated marginally less footpad swelling in response to intradermal injection of KLH. Interestingly, significantly higher levels of KLH-specific IgG (p < 0.05) and IgM (p < 0.01) were found in the serum of mice injected with CXCR5-BMDC compared with mice immunized with vector-transduced BMDC. Thus, CXCR5 is predominantly expressed by dermal-type DC. Moreover, CXCR5 directs BMDC to BCZ of LN in vivo and modifies Ag-specific immune responses induced by BMDC vaccination.