RESUMEN
Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process. Also, it has been reported to be associated with the onset of various cancers. An effective anti-inflammatory drug should be able to inhibit the development of inflammation without interfering in normal homeostasis. Current approaches to overcome the inflammation include the use of immune selective anti-inflammatory derivatives, selective glucocorticoid receptor agonist, resolvins and protectins and TNF inhibitors. A number of herbal drugs have been identified in the past that can target inflammatory cytokines. This review mainly focuses on the newer molecules to combat the inflammation and also emphasise on various studies carried out in the past. Thus, the high prevalence of inflammation obliges the development of new drugs; therefore, a safe and efficient drug molecule to confer protection against inflammation is urgently needed.
Asunto(s)
Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico , Anexina A1/biosíntesis , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Eicosanoides/biosíntesis , Ácido Eicosapentaenoico/análogos & derivados , Glucocorticoides/farmacología , Glucocorticoides/uso terapéutico , Humanos , Mediadores de Inflamación/metabolismo , Dolor/tratamiento farmacológico , Plantas Medicinales , Receptores de Glucocorticoides/agonistas , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Elevated cyclooygenase-2 (COX-2) expression is frequently observed in human non-small cell lung cancer (NSCLC) and associated with poor prognosis, indicating critical involvement of the inflammatory pathway in lung carcinogenesis. Recently, we found that green tea extract (GTE) induced Annexin-1 (ANX1) in the lung adenocarcinoma A549 cells. ANX1 is a glucocorticoid-inducible 37kDa protein involved in a wide range biological function and is an important anti-inflammatory mediator. The present study further examines the interplay between the expressions and production of ANX1, COX-2, phospholipase A(2) (cPLA(2)) and prostaglandin E(2) (PGE(2)) following the treatment of NSCLC cell lines with GTE. We found that GTE induced ANX1 and inhibited COX-2 expression in lung cancer A549, H157 and H460 cell lines. Addition of pro-inflammatory cytokine IL-1ß diminished GTE-induced ANX1. Silence of ANX1 in cells abrogates the inhibitory activity on COX-2, indicating that the anti-inflammatory activity of GTE is mediated at least partially by the up-regulation of ANX1. However, differential pattern of inhibitory effects of ANX1 on cPLA(2) expression was observed among various cell types, suggesting that the anti-inflammatory activity mediated by ANX1 is cell type specific. Our study may provide a new mechanism of GTE on the prevention of lung cancer and other diseases related to inflammation.
Asunto(s)
Anexina A1/biosíntesis , Camellia sinensis/química , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Inhibidores de la Ciclooxigenasa 2/farmacología , Ciclooxigenasa 2/metabolismo , Neoplasias Pulmonares/enzimología , Fosfolipasas A2 Citosólicas/química , Extractos Vegetales/farmacología , Línea Celular Tumoral , Dinoprostona , Humanos , Concentración 50 InhibidoraRESUMEN
Resveratrol (3,4',5-trihydroxy-trans-stilbene), one of secondary metabolites of low molecular weight present in plant, has various important biological effects. It can induce apoptosis in human leukemia cell types in vitro, although the mechanism is not fully understood. In the present study, we demonstrated reduced viability and DNA synthesis, as well as increased proportion of the subdiploid cell population, in HL-60 cells as determined by cell cycle analysis with resveratrol. Resveratrol treatment resulted in a gradual time-dependent decrease in the expression of anti-apoptotic Bcl-2 and increase in that of Bax, annexin A1, growth arrest- and DNA damage-induced gene 45α (GADD45α), and cleaved caspase-3. In addition, resveratrol markedly increased caspase-3 activity in cells. Our results suggest that resveratrol could inhibit the proliferation and induce apoptosis of HL-60 cells through a GADD45α and annexin A1/caspase-3 pathway.
Asunto(s)
Anexina A1/metabolismo , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Proteínas de Ciclo Celular/metabolismo , Proteínas Nucleares/metabolismo , Estilbenos/farmacología , Anexina A1/biosíntesis , Anexina A1/genética , Apoptosis/fisiología , Caspasa 3/metabolismo , Proteínas de Ciclo Celular/biosíntesis , Proteínas de Ciclo Celular/genética , Procesos de Crecimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Daño del ADN , Fase G1/efectos de los fármacos , Células HL-60 , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Proteínas Nucleares/biosíntesis , Proteínas Nucleares/genética , Inhibidores de la Síntesis del Ácido Nucleico/farmacología , Fase de Descanso del Ciclo Celular/efectos de los fármacos , ResveratrolRESUMEN
Cytokines, such as granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-8 attract neutrophils into inflammatory sites. During emigration from the blood neutrophils interact with extracellular matrix proteins such as fibronectin. Fibronectin provides beta2-integrin co-stimulation, allowing GM-CSF and IL-8 to activate nuclear factor (NF)-kappaB, an effect that does not occur in suspension. We tested the hypothesis that exposure of mice to fever-like temperatures abrogates neutrophil recruitment and NF-kappaB activation in a mouse model of skin inflammation. Mice that were exposed to 40 degrees C for 1 hour showed strongly reduced GM-CSF- and IL-8-induced neutrophilic skin inflammation. In vitro heat exposure did not interfere with neutrophil adhesion or spreading on fibronectin but strongly inhibited migration toward both cytokines. Using specific inhibitors, we found that PI3-K/Akt was pivotal for neutrophil migration and that heat down-regulated this pathway. Furthermore, neutrophils on fibronectin showed abrogated NF-kappaB activation in response to GM-CSF and IL-8 after heat. In vivo heat exposure of mice followed by ex vivo stimulation of isolated bone marrow neutrophils confirmed these results. Finally, less NF-kappaB activation was seen in the inflammatory lesions of mice exposed to fever-like temperatures as demonstrated by in situ hybridization for IkappaBalpha mRNA. These new findings suggest that heat may have anti-inflammatory effects in neutrophil-dependent inflammation.
Asunto(s)
Citocinas/inmunología , Hipertermia Inducida , Inflamación/inmunología , FN-kappa B/metabolismo , Infiltración Neutrófila/inmunología , Animales , Anexina A1/biosíntesis , Apoptosis/fisiología , Western Blotting , Adhesión Celular , Células Cultivadas , Quimiotaxis de Leucocito/inmunología , Citocinas/metabolismo , Ensayo de Cambio de Movilidad Electroforética , Activación Enzimática/fisiología , Citometría de Flujo , Calor , Humanos , Hibridación in Situ , Inflamación/metabolismo , Integrina beta3/biosíntesis , Ratones , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/biosíntesis , Receptores de Interleucina-8/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , TiempoRESUMEN
The appearance of immunoreactive interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha, prostaglandin (PG) E2 and lipocortin-1 in the central nervous system was investigated during the development of lesions in a 301V/VM murine scrapie model. Focal PrP(Sc) deposition was present after 30 days of the 115-120 day incubation period; this immunoreactivity increased in intensity and distribution thereafter. Staining for IL-1beta and TNF alpha in perivascular macrophages, and PGE2 immunoreactivity in astrocytes, was detected in those areas showing PrP(Sc) deposition from 60 days. Increased GFAP and F4/80 immunoreactivity, indicating activation of astrocytes and microglia, was also evident in these areas from 60 days. Glial cytokine and lipocortin immunoreactivity was detected after 90 days, in the absence of clinical signs. The disease-induced cytokine, PG and lipocortin immunoreactivity occurred only in those brain areas showing PrP(Sc) deposition, glial activation and, in later stages, vacuolation. These findings support the concept that PrP(Sc) deposition induces glial cytokine production. These glial cytokines may contribute to the development of the pathological lesions in scrapie.
Asunto(s)
Anexina A1/biosíntesis , Encéfalo/metabolismo , Citocinas/biosíntesis , Dinoprostona/metabolismo , Scrapie/fisiopatología , Animales , Encéfalo/inmunología , Encéfalo/patología , Proteína Ácida Fibrilar de la Glía/análisis , Hipocampo/inmunología , Hipocampo/metabolismo , Hipocampo/patología , Inmunohistoquímica , Interleucina-1/biosíntesis , Interleucina-6/biosíntesis , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Ratones Endogámicos , Priones/biosíntesis , Scrapie/inmunología , Scrapie/metabolismo , Tálamo/inmunología , Tálamo/metabolismo , Tálamo/patología , Factores de Tiempo , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Thymic epithelial cell line TEA3A1 produce prostaglandin E2 (PGE2) and express high levels of annexin I. In order to study the relationship between the levels of annexin I expression and the arachidonic acid metabolism, TEA3A1 cells transfected with expression vector containing full length annexin I cDNA in either sense or anti-sense orientation was studied. In the anti-sense cells where the level of annexin I was reduced, the PGE2 production was significantly lower. On the other hand, PGE2 production was significantly higher in sense cells where the production of annexin I was also higher than in control cells. Our results show that increased PGE2 production in sense cells was accompanied by higher levels of PLA2 enzymatic activities. These results suggest that the production of annexin I is positively associated with the phospholipase A2 enzymatic activity and the prostaglandin production in thymic epithelial cells.