The NF-κB RelA transcription factor is not required for CD8+ T-cell function in acute viral infection and cancer.

CD8+ T cells are critical mediators of pathogen clearance and anti-tumor immunity. Although signaling pathways leading to the activation of NF-κB transcription factors have crucial functions in the regulation of immune responses, the CD8+ T cell-autonomous roles of the different NF-κB subunits, are still unresolved. Here, we investigated the function of the ubiquitously expressed transcription factor RelA in CD8+ T-cell biology using a novel mouse model and gene-edited human cells. We found that CD8+ T cell-specific ablation of RelA markedly altered the transcriptome of ex vivo stimulated cells, but maintained the proliferative capacity of both mouse and human cells. In contrast, in vivo experiments showed that RelA deficiency did not affect the CD8+ T-cell response to acute viral infection or transplanted tumors. Our data suggest that in CD8+ T cells, RelA is dispensable for their protective activity in pathological contexts.

Ex vivo Immuno-modulatory effect of Echinococcus granulosus laminated layer during allergic rhinitis and allergic asthma: A study in Algerian Patients.

The effect of helminthic infections on allergic diseases and asthma is still inconclusive. Moreover, there is considerable evidence suggesting that nitric oxide (NO), metalloproteinases and pro-inflammatory cytokines play a significant role in the physiopathology of these diseases. In this sense, the aim of our study is to investigate the ex vivo immunomodulatory effect of the laminated layer (LL, outside layer of parasitic cyst) of the helminth Echinococcus granulosus on NO, IL-17A and IL-10 production. In the first step of our study, we evaluated in vivo the NO, MMP-9, IL-17A, IL-10 levels in Algerian patients with allergic asthma and allergic rhinitis and their changes in relation with exacerbation status of the patients. In the principal part of our work, we assessed NO, IL-10 and IL-17A levels in supernatants of patients PBMC cultures before and after stimulation with LL. Our results indicate a significant reduction in NO production by PBMC of patients with allergic rhinitis and allergic asthma whether mild, moderate or severe after stimulation with LL. Interestingly, LL induces a significant decrease in the production of NO and IL17-A levels as well as an increase in the production of IL-10 in the cultures performed with PBMC of patients with severe allergic asthma. Importantly, our data indicate that LL exert a down-modulatory effect on inflammatory mediators (NO, IL-17A) and up immune-regulatory effect on IL-10 production. Collectively, our study supports the hygiene hypothesis suggesting that Echinococcus granulosus infection like other helminths could prevent and/or modulate inflammation responses during inflammatory diseases.

Beneficial role of Pistacia lentiscus aqueous extract in experimental colitis: anti-inflammatory and potential therapeutic effects.

BACKGROUND: Pistacia lentiscus L. (PL) is a flowering plant traditionally used in the treatment of gastrointestinal disorders. The extracts of this plant are endowed with strong pharmacological activities. The aim of our current study was to investigate the anti-inflammatory and potential therapeutic effects of PL leaves aqueous extract (PLAE) against Dextran Sulfate Sodium (DSS)-induced acute colitis. MATERIALS AND METHODS: The therapeutic effect of PLAE was evaluated after orally administration of 3% DSS alone or concomitantly with PLAE (50, 100 or 200 mg/Kg). Mucosal lesions were assessed by macroscopic and histopathological examination. In this context, hemorrhage, diarrhea, weight loss, and disease activity index (DAI) were determined daily throughout the experiment. In the same way, hematoxylin-eosin and Alcian blue staining of colonic mucosal were used to evaluate, respectively, mucosal damages and mucus production. Furthermore, the levels of nitric oxide (NO), and pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] were measured in plasma, as well as in colonic explants and peritoneal macrophages cultures supernatants. RESULTS: Administration of DSS + PLAE indicated a significant reduction in clinical score of acute colitis DAI compared to DSS alone administration. Interestingly, histological analysis of the mucosa showed that DSS + PLAE-treated groups exhibited almost normal histology evidenced by an intact epithelium structure and less inflammatory cell infiltration in the mucosa. Alcian bleu staining revealed that DSS + PLAE-treated groups displayed almost normal mucus production. Importantly, a significant decrease in pro-inflammatory mediators (NO, IL-6 and TNF-α) levels in dose-dependent manner was reported in plasma, and culture supernatants of colonic explants and peritoneal macrophages from DSS + PLAE-treated mice compared to the DSS group. CONCLUSION: Our results showed that the systemic and local anti-inflammatory activities of aqueous leaves extract of PL improve the clinical signs of acute colitis. Our data suggest that PLAE has beneficial effects and could constitute a promising approach against acute ulcerative colitis by targeting the deregulated immune response.

Gastro-protective, therapeutic and anti-inflammatory activities of Pistacia lentiscus L. fatty oil against ethanol-induced gastric ulcers in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Pistacia lentiscus L. (Anacardiaceae) (PL) is a flowering plant that grows in the Mediterranean area. It is traditionally used in the treatment of various skin, respiratory and gastrointestinal disorders AIM OF THE STUDY: In the present study, we investigated the anti-ulcerogenic activity of Pistacia lentiscus fatty oil (PLFO) on ethanol-induced gastric ulcers in Wistar rats MATERIAL AND METHODS: PLFO was orally administered to two experimental groups of rats before or after ethanol induction of gastric ulcer. The lesions of the gastric mucosa were evaluated by macroscopic and histopathological examination. In addition, the amount of nitric oxide (NO) and pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the supernatant from cultures of gastric mucosa explants were assessed. Finally, the mucus production and iNOS (inducible NO synthase) expression were determined by histochemical and immunohistochemical analysis, respectively RESULT: Our results indicated that the PLFO pretreatment or PLFO treatment significantly reduced ulcerated and hemorrhagic areas. Additionally, pretreatment or treatment with PLFO after ethanol-induced ulceration significantly reduced the plasma concentration of NO. Furthermore, a significant decrease of NO, IL-6 and TNF-α levels was observed in explant culture supernatants. iNOS expression was also reduced in the gastric mucosa. In contrast, mucus production by goblet cells was enhanced. Interestingly, histological analysis of the gastric mucosa has indicated that PLFO- pretreated and treated groups displayed normal histology CONCLUSION: Our results demonstrate that PLFO display significant prophylactic and therapeutic effects against gastric ulcers. Importantly, the mechanism underlying PLFO activities might implicate inhibition of inflammatory responses during gastric ulcer.