RESUMO
The Yusho poisoning incident, caused by rice oil contaminated with polychlorinated biphenyls (PCBs), polychlorinated quarterphenyls (PCQs), and polychlorinated dibenzofurans (PCDFs) generated by heat-denatured PCBs, occurred in 1968 in western Japan. Although severe symptoms are rarely observed today, the levels of PCBs and PCDFs in the sera of Yusho patients remain high. The aryl hydrocarbon receptor (AhR), which also acts as a dioxin receptor, is a transcriptional regulator that mediates dioxin toxicity. Recent studies show that dioxin mediates its immune toxic effects via AhR and that AhR activation induces dysregulation of interleukin (IL)-17- producing T (TH17) cells. This study therefore hypothesized that Yusho patients would show dysregulated TH17 cell-mediated immune responses. To validate the hypothesis, levels of IL-17 and IL-22, each secreted by TH17 cells, along with IL-1ß and IL-23 were measured in serum samples from 40 Yusho patients and 40 age-matched controls. Levels of tumor necrosis factor (TNF)-α potentially secreted by TH17 cell-stimulated neutrophils and macrophages were also measured. The results indicated that serum IL-17 levels, as well as those of IL-1ß, IL-23, and TNFα, were significantly higher in Yusho patients than in controls. In contrast, serum IL-22 levels were significantly lower in the Yusho patients. These results suggest that Yusho patients have dysregulated TH17 cell-mediated immune responses that may be linked to inflammation.
Assuntos
Contaminação de Alimentos , Inflamação/imunologia , Macrófagos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Benzofuranos/toxicidade , Células Cultivadas , Clorobenzenos/toxicidade , Citocinas/sangue , Dibenzofuranos Policlorados , Feminino , Humanos , Inflamação/induzido quimicamente , Japão , Macrófagos/imunologia , Masculino , Neutrófilos/imunologia , Bifenilos Policlorados/toxicidade , Receptores de Hidrocarboneto Arílico , Células Th17/imunologia , Regulação para CimaRESUMO
H2S has been highlighted recently as an endogenous, gaseous signaling molecule, especially in inflammations. The deposition of IC induces an acute inflammatory response with tissue injury. To assess the roles of H2S in the IC-induced diseases, the cutaneous, reverse passive Arthus reaction was conducted using NaHS as a H2S donor. Furthermore, we conducted similar experiments using selectin(-/-) mice to determine the involvement of selectin molecules in the H2S-mediated pathway. Exogenous application of NaHS dramatically attenuated inflammatory reactions in WT mice associated with Arthus reaction. Namely, mRNA expressions of TNF-α, IFN-γ, and neutrophil numbers were reduced significantly in the lesional skins of NaHS-treated WT mice relative to untreated ones. NaHS treatment significantly reduced these three parameters in the lesional skins of E- and P-selectin(-/-) mice but not in those of L-selectin(-/-) mice. Quite similar results were obtained in the blocking study using WT mice injected with mAb to E-, P-, and L-selectin. Our results indicated that the exogenous application of NaHS attenuates inflammatory responses in reverse passive Arthus reaction through a L-selectin-involved pathway but not through E- or P-selectin pathways.
Assuntos
Reação de Arthus/prevenção & controle , Sulfeto de Hidrogênio/farmacologia , Selectina L/imunologia , RNA Mensageiro/sangue , Pele/efeitos dos fármacos , Sulfetos/farmacologia , Animais , Anticorpos/farmacologia , Complexo Antígeno-Anticorpo/imunologia , Reação de Arthus/genética , Reação de Arthus/imunologia , Reação de Arthus/patologia , Selectina E/genética , Selectina E/imunologia , Deleção de Genes , Expressão Gênica , Sulfeto de Hidrogênio/metabolismo , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Inflamação/prevenção & controle , Interferon gama/biossíntese , Interferon gama/imunologia , Selectina L/genética , Masculino , Camundongos , Camundongos Knockout , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/patologia , Selectina-P/genética , Selectina-P/imunologia , RNA Mensageiro/genética , Transdução de Sinais/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Sulfetos/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologiaRESUMO
CD163 is a 130-kDa, type I transmembrane protein belonging to group B of the cysteine-rich scavenger receptor family. Expression of CD163 is constitutive and/or induced by some stimuli on circulating monocytes and most tissue macrophages. An approximately 130-kDa soluble form of human CD163 is released from the cell surface by proteolysis after oxidative stress or inflammatory stimuli. Thus, an elevated level of circulating soluble CD163 (sCD163) has been reported in diabetes mellitus, which is one of the oxidative conditions. We have already acknowledged that scleroderma (SSc) is one of the oxidative conditions. Therefore, we conducted the measurement of serum sCD163 in SSc patients. After receiving the informed consents, 56 SSc patients were examined; 20 dermatomyositis patients were used as disease controls and 40 persons were used as healthy controls. Blood samples were collected, and the concentration of serum sCD163 was measured by ELISA (human CD163, R&D Systems). Other parameters in the blood of SSc patients were also examined. Statistical analyses were performed using Mann-Whitney U test, and the relationship between parameters was statistically examined by Spearman's rank test. Serum sCD163 levels were elevated in SSc patients compared with normal controls (p < 0.01), with similar levels between limited SSc and diffuse SSc patients. SSc patients with pulmonary fibrosis had increased serum levels of sCD163 than those without pulmonary fibrosis (p < 0.05). SSc patients with elevated sCD163 levels had increased serum levels of IgG than those with normal sCD163 levels (p < 0.05). Serum sCD163 levels correlated positively with pulsatility index in SSc patients (p = 0.0009, r = 0.534). These results suggest that oxidative stress may play an important role in immunological abnormalities, renal circulation, and pulmonary fibrosis of SSc.
Assuntos
Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Fibrose Pulmonar/sangue , Receptores de Superfície Celular/sangue , Escleroderma Sistêmico/sangue , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/complicações , Fibrose Pulmonar/imunologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/imunologiaRESUMO
BACKGROUND: Malignant melanoma is often accompanied by a host response of inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. OBJECTIVE: To evaluate the role of adhesion molecules, including P-selectin glycoprotein ligand-1 (PSGL-1), P-selectin, and E-selectin. METHODS: Subcutaneous primary growth and metastasis to the lung of B16 melanoma cells were examined in mice lacking PSGL-1, P-selectin, or E-selectin. RESULTS: Primary subcutaneous growth of B16 melanoma was augmented by loss of PSGL-1, P-selectin, or E-selectin, while pulmonary metastasis was reduced by the loss of E-selectin. The enhancement of subcutaneous tumor growth was associated with a reduced accumulation of natural killer cells, CD4(+) T cells and CD8(+) T cells, while the attenuation of pulmonary metastasis was related to the numbers of CD8(+) T cells. The expressions of transforming growth factor (TGF)-ß and interleukin (IL)-6 were correlated with primary subcutaneous growth; TGF-ß, IL-6, and interferon-γ were related to number of metastatic lung nodules. Cytotoxicity against melanoma cells in splenocytes and in tumor-draining lymph node cells were not defective by the absence of adhesion molecules, suggesting that the enhancement of tumor growth and metastasis caused by the loss of selectins results from an impaired migration of effector cells into the tissue. CONCLUSIONS: The results indicate the complexity of anti-tumor responses mediated by adhesion molecules in primary subcutaneous tumors and pulmonary metastasis of murine experimental melanoma.
Assuntos
Selectina E/fisiologia , Melanoma Experimental/etiologia , Glicoproteínas de Membrana/fisiologia , Selectina-P/fisiologia , Neoplasias Cutâneas/etiologia , Animais , Citocinas/genética , Leucócitos/fisiologia , Neoplasias Pulmonares/secundário , Masculino , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/análise , Neoplasias Cutâneas/patologiaRESUMO
Stress affects the pathophysiology of cutaneous immune reactions, including contact hypersensitivity (CH) in individuals sensitized with sensitizing hapten, where local endothelial cell activation plays a critical role. To clarify the effects of stress in cutaneous immune reactions, we selected a CH model using annoying sound as a stress. Furthermore, we conducted the stress experiments by using selectin-deficient mice to determine the involvement of selectin molecules regarding local endothelial activation. Auditory stress augmented CH responses in the present study. Namely, ear thickness and mast cell numbers were significantly increased in stressed CH mice. mRNA expression of preprotachykinin-A, a precursor of substance-P; interferon-gamma; interleukin (IL)-4; IL-6; and tumor necrosis factor-alpha significantly increased in stressed CH mice. Furthermore, stressed L-selectin-deficient mice showed significant decreases in all parameters mentioned above relative to stressed wild-type mice in CH response. Meanwhile, treatment with anti-L-selectin Ab resulted in a significant decrease in ear thickness and mRNA levels of interferon-gamma, IL-4, IL-6, and tumor necrosis factor-alpha, but failed to significantly reduce preprotachykinin-A mRNA levels and mast cell numbers. Our results indicated that auditory stress enhances CH response and that the augmentation of this CH response might be mediated through L-selectin, but not through P- or E-selectin pathways.