Candesartan inhibits inflammation through an angiotensin II type 1 receptor independent way in human embryonic kidney epithelial cells.

Besides stimulating vasoconstriction, Angiotensin II is also well known in inducing reactive oxygen species and promoting inflammatory phenotype switch via its type 1 receptor. In clinic, Angiotensin II type 1 (AT1) receptor blocker like candesartan has been widely applied as an antihypertensive medication. We previous have demonstrated that a higher dose of candesartan plays a protective role after kidney injury. However, whether candesartan could exhibit anti-inflammatory effects remains unclear. Here, by stimulating isolated human embryonic kidney epithelial cells with tumor necrosis factor-α (TNF-α), we observed the anti-inflammation capacity of candesartan ex vivo. It was found that pre-treat with candesartan significantly suppressed transforming growth factor-ß (TGF-ß) and interleukin-6 (IL-6) expression after incubation with TNF-α. Surprisingly, silence of angiotensin II type 1 receptor has little effects on reducing TGF-ß or IL-6 products. Furthermore, candesartan inhibited TNF-α-induced oxidative stress in the primary cultured tubular epithelial cells. Overall, our data indicates that candesartan suppresses TNF-α-induced inflammatory cytokine production by inhibiting oxidative stress, rather than block AT1 receptor activity.

Differential cytokine expression by human dendritic cells in response to different Porphyromonas gingivalis capsular serotypes.

AIM: Capsular polysaccharides play an important role in the virulence of Gram-positive and Gram-negative bacteria. In Porphyromonas gingivalis, six serotypes have been described based on capsular antigenicity and its pathogenicity has been correlated both in vitro and in animal models. This study aimed to investigate the differential response of human dendritic cells (DCs) when stimulated with different P. gingivalis capsular serotypes. MATERIALS AND METHODS: Using different multiplicity of infection (MOI) of the encapsulated strains K1-K6 and the non-encapsulated K(-) strain of P. gingivalis, the mRNA expression levels for interleukin (IL)-1beta, IL-2, IL-5, IL-6, IL-10, IL-12, IL-13, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, and TNF-beta in stimulated DCs were quantified by real-time reverse transcription-polymerase chain reaction. RESULTS: All P. gingivalis capsular serotypes induced a T-helper type 1 (Th1) pattern of cytokine expression. K1- and K2-stimulated DCs expressed higher levels of IL-1beta, IL-6, IL-12p35, IL-12p40, and IFN-gamma and at lower MOI than DCs stimulated with the other strains. CONCLUSIONS: These results demonstrate a differential potential of P. gingivalis capsular serotypes to induce DC responses and a higher capacity of strains K1 W83 and K2 HG184 than other K serotypes to trigger cytokine expression.

Over-expression of forkhead box P3 and its association with receptor activator of nuclear factor-kappa B ligand, interleukin (IL) -17, IL-10 and transforming growth factor-beta during the progression of chronic periodontitis.

AIM: T regulatory (Treg) cells have been detected in periodontitis lesions, and forkhead box P3 (Foxp3) expression has been negatively correlated to receptor activator of nuclear factor-kappa B ligand (RANKL). The aim of this study was to correlate T-helper type 1 (Th1), Th2, Th17 and Treg transcription factor expressions, in gingival tissues from patients undergoing active periodontal tissue destruction, with bone loss-associated cytokines. MATERIALS AND METHODS: In 10 chronic periodontitis patients undergoing disease progression, the mRNA expressions of T-bet, GATA-3, Foxp3, RORC2, interleukin (IL)-1beta, IL-10, IL-17, RANKL, interferon (IFN)-gamma and transforming growth factor (TGF)-beta1 were quantified using real-time reverse transcription-polymerase chain reaction. The levels of these markers were compared between active and inactive periodontal lesions. RESULTS: In active periodontal lesions, Foxp3, T-bet, RANKL, IL-17, IL-1beta and IFN-gamma were significantly over-expressed compared with inactive lesions. The expression of IFN-gamma was the highest within the active periodontal lesions, similar to that of TGF-beta1 within the inactive ones. There was a positive correlation between RANKL and IL-17. Additionally, RANKL and IL-17 were positively correlated with RORC2, but no correlation was detected with Foxp3. CONCLUSIONS: These results lead us to speculate that Foxp3(+) cells that do not have a regulatory function might have a role in the pathogenesis of active periodontal lesions by down-regulating TGF-beta1 and IL-10 synthesis that lead to the over-expression of Th17-associated cytokines RANKL and IL-17.

Immunolocalization of interleukin 4, interleukin 6, and lymphotoxin alpha in dental granulomas.

OBJECTIVE: The purpose of this study was to determine the immunolocalization of the interleukin (IL) 4, IL-6, and lymphotoxin (LT) alpha in dental granulomas and correlate their expression with the intensity of the inflammatory infiltrate. Study design Fifteen paraffin specimens of dental granulomas were selected, and the streptavidin-biotin complex stain was used to detect IL-4, IL-6, and LT-alpha. RESULTS: Our results revealed a significant statistical correlation between the intensity of inflammatory infiltrate and the percentage of mononuclear cells positive for IL-4. Moreover, we observed a statistically significant correlation between the frequency of cells expressing IL-6 and LT-alpha. CONCLUSION: These data suggest that the predominance of a helper T cell subtype 2 response in dental granulomas is correlated with the exacerbation of the inflammatory reaction and its evolution. Moreover, a correlation between the frequency of IL-6-positive and LT-alpha-positive cells suggests that the synergistic activities of these 2 cytokines may be involved in the pathogenesis of this inflammatory condition.

Incidência de pacientes hipersensibilizados em lista de espera contra doador cadáver / Incidence of hypersencitized patients in waiting lists for cadaver donois

Cento e vinte pacientes em programa crônico de diálise (38,8 = 17,3 meses) a espera de transplante renal em lista de doador cadáver foram analisados quanto ao grau de infocitotoxicidade contra um painel selecionado de 22 células HLA (A, B) tipadas e fixas. Os pacientes foram distribuídos em três grupos quanto ao nível de sensibilizaçäo (0-9,9%, 10-49,9% e acima de 50%). O número de pacientes em cada nível foi de 61 (49%), 33 (26%) respectivamente. O sexo femenino significativamente superior no grupo de hipersensibilidados (> 50%) e o sexo masculino no de näo sensibilizados (0-9,9%). As gestaçöes prévias parecem ter contribuido para este caráter de hiperreatividade. Näo ocorreu um percentual crescente de hipersensibilizados a medida que se prolongava o tempo em diálise, estando o grupo hipersensibilizados já precocemente definido nos primeiros seis meses de diálise. No grupo de pacientes com mais de um painel, o grau de sensibilizaçäo permaneceu estável em 65% e nos restantesfoi observado uma tendência a elevaçäo e, 17,4%, a queda em 5,8*, e um comportamento errático em 11,8%