RESUMO
The ovine choroid plexus (ChP) expresses the long isoform of the leptin receptor, which makes this structure a potential target for leptin action. In sheep, leptin concentration in plasma is higher during long days (LD) than short days (SD). This study evaluates the influence a of photoperiod on leptin impact on the gene expression of Toll-like receptor 4 (TLR4), proinflammatory cytokines (IL1B, IL6), their receptors (IL1R1, IL1R2, ILRN, IL6R, IL6ST) and inflammasome components necessary for pro-IL-1ß activation (NLRP3, PYCARD, CASP1), chemokine (CCL2), leptin receptor isoforms (LEPRa, LEPRb) and a suppressor of cytokine signalling (SOCS3) in the ChP of ewes treated or not with lipopolysaccharide (LPS). Studies were conducted on adult female sheep divided into four groups (n = 6 in each): control, leptin (20 µg/kg), LPS (400 ng/kg), and LPS and leptin injected under SD and LD photoperiods. The leptin alone did not affect the gene expression but in co-treatment with LPS increased (p < 0.05) IL1B but only during SD, and SOCS3, IL1R2, IL1RN, IL6ST and CCL2 only during LD, and decreased (p < 0.05) the IL1R1 expression only during SD photoperiod. This indicates that the immunomodulatory action of leptin on the ChP is manifested only under the LPS challenge and is photoperiodically dependent.
Assuntos
Plexo Corióideo/metabolismo , Inflamassomos/metabolismo , Leptina/sangue , Fotoperíodo , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Plexo Corióideo/efeitos dos fármacos , Feminino , Inflamassomos/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Ovinos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
Previous studies suggest that coinfection of leprosy and human immunodeficiency virus (HIV) does not decrease the frequency and intensity of leprosy reactions. However, the immunological aspects of leprosy reactions in coinfected patients remain obscure, with a limited number of studies showing contradictory results. Observational study using tissue samples collected during leprosy reactions from 15 patients coinfected with leprosy and HIV and from 15 patients with leprosy alone. Patients were part of a prior larger cohort study of leprosy patients with and without HIV coinfection. Specific antibodies were used to detect IL-1ß and IL-6 expression in skin biopsy tissue cells. IL-1ß and IL-6 expression was similar between leprosy patients with and without HIV coinfection (p>0.05). Coinfected and non-coinfected tissues showed similar levels of IL-1ß and IL-6 expression for type 1 reactions. A trend towards increased levels of IL-1ß and IL-6 expression was observed in tissue from coinfected patients (p=0.0024). The expression of IL-1ß and IL-6 during leprosy reactions did not differ significantly between tissues obtained from leprosy patients with and without HIV coinfection. Therefore, we conclude that HIV coinfection does not affect the immunological pattern of leprosy reactions.
Assuntos
Coinfecção/metabolismo , Infecções por HIV/complicações , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Hanseníase/complicações , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Regulação da Expressão Gênica/imunologia , Infecções por HIV/imunologia , Humanos , Imuno-Histoquímica , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Hanseníase/imunologia , Modelos Lineares , Masculino , Pele/patologiaRESUMO
Neutrophil recruitment is pivotal to the host defense against microbial infection, but it also contributes to the immunopathology of disease. We investigated the mechanism of neutrophil recruitment in human infectious disease by means of bioinformatic pathways analysis of the gene expression profiles in the skin lesions of leprosy. In erythema nodosum leprosum (ENL), which occurs in patients with lepromatous leprosy and is characterized by neutrophil infiltration in lesions, the most overrepresented biological functional group was cell movement, including E-selectin, which was coordinately regulated with interleukin 1beta (IL-1beta). In vitro activation of Toll-like receptor 2 (TLR2), up-regulated in ENL lesions, triggered induction of IL-1beta, which together with interferon gamma induced E-selectin expression on and neutrophil adhesion to endothelial cells. Thalidomide, an effective treatment for ENL, inhibited this neutrophil recruitment pathway. The gene expression profile of ENL lesions comprised an integrated pathway of TLR2 and Fc receptor activation, neutrophil migration, and inflammation, providing insight into mechanisms of neutrophil recruitment in human infectious disease.