Circulating levels of monocytic myeloid-derived suppressor cells (M-MDSC) and CXCL-8 in non-small cell lung cancer (NSCLC)

BACKGROUND: Myeloid-derived suppressor cells (MDSC) are categorized as granulocytic (G-MDSCs) and monocytic (M-MDSCs) and their expansion play a role in cancer progression. Recruitment to the cancer site depends upon the presence of a chemoattractant. We aimed to investigate the presence of MDSC subtypes and of interleukin-8 (CXCL-8) in the peripheral blood in lung cancer subtypes including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients. MATERIALS AND METHODS: Peripheral blood samples of 26 NSCLC patients, 18 SCLC patients, and 8 healthy control donors (HDs) were harvested and the surface expression of CD14, CD15, CD11b, and HLA-DR on MDSCs was measured using flow cytometry. The level of serum CXCL8 was measured by the ELISA method. RESULTS: The frequency of circulating M-MDSCs was significantly higher in patients with NSCLC than in SCLC and HDs. In contrast, there was no statistical difference concerning the frequency of circulating G-MDSCs between the three groups. The concentration of CXCL-8 was significantly higher in the NSCLC and SCLC patients than in HD control with no significant difference between NSCLC and SCLC groups. There was no correlation between serum CXCL8 and G-MDSC levels. CONCLUSION: Our data confirm a higher frequency of circulating M-MDSCs, but not G-MDSCs, in the blood of those suffering from NSCLC but not for SCLC cases. Measuring MDSC subtypes and serum chemotactic factors may have implications for the differential diagnosis of NSCLC

Conjugated Alpha-Alumina nanoparticle with vasoactive intestinal peptide as a Nano-drug in treatment of allergic asthma in mice

Asthma is a chronic respiratory disease characterized by airway inflammation, bronchoconstriction, airway hyperresponsiveness and recurring attacks of impaired breathing. Vasoactive intestinal peptide (VIP) has been proposed as a novel anti-asthma drug due to its effects on airway smooth muscle relaxation, bronchodilation and vasodilation along with its immunomodulatory and anti-inflammatory properties. In the current study, we investigated the therapeutic effects of VIP when conjugated with α-alumina nanoparticle (α-AN) to prevent enzymatic degradation of VIP in the respiratory tract. VIP was conjugated with α-AN. Balb/c mice were sensitized and challenges with ovalbumin (OVA) or PBS and were divided in four groups; VIP-treated, α-AN-treated, α-AN-VIP-treated and beclomethasone-treated as a positive control group. Specific and total IgE level, airway hyperresponsiveness (AHR), bronchial cytokine expression and lung histology were measured. α-AN-VIP significantly reduced the number of eosinophils (Eos), serum IgE level, Th2 cytokines and AHR. These effects of α-AN-VIP were more pronounced than that seen with beclomethasone or VIP alone (P<0.05). The current data indicate that α-AN-VIP can be considered as an effective nano-drug for the treatment of asthma

Anti-Inflammatory Role of the cAMP Effectors Epac and PKA: Implications in Chronic Obstructive Pulmonary Disease

Cigarette smoke-induced release of pro-inflammatory cytokines including interleukin-8 (IL-8) from inflammatory as well as structural cells in the airways, including airway smooth muscle (ASM) cells, may contribute to the development of chronic obstructive pulmonary disease (COPD). Despite the wide use of pharmacological treatment aimed at increasing intracellular levels of the endogenous suppressor cyclic AMP (cAMP), little is known about its exact mechanism of action. We report here that next to the β2-agonist fenoterol, direct and specific activation of either exchange protein directly activated by cAMP (Epac) or protein kinase A (PKA) reduced cigarette smoke extract (CSE)-induced IL-8 mRNA expression and protein release by human ASM cells. CSE-induced IκBα-degradation and p65 nuclear translocation, processes that were primarily reversed by Epac activation. Further, CSE increased extracellular signal-regulated kinase (ERK) phosphorylation, which was selectively reduced by PKA activation. CSE decreased Epac1 expression, but did not affect Epac2 and PKA expression. Importantly, Epac1 expression was also reduced in lung tissue from COPD patients. In conclusion, Epac and PKA decrease CSE-induced IL-8 release by human ASM cells via inhibition of NF-κB and ERK, respectively, pointing at these cAMP effectors as potential targets for anti-inflammatory therapy in COPD. However, cigarette smoke exposure may reduce anti-inflammatory effects of cAMP elevating agents via down-regulation of Epac1

Interaction of Pattern Recognition Receptors with Mycobacterium Tuberculosis.

Tuberculosis (TB) is considered a major worldwide health problem with 10 million new cases diagnosed each year. Our understanding of TB immunology has become greater and more refined since the identification of Mycobacterium tuberculosis (MTB) as an etiologic agent and the recognition of new signaling pathways modulating infection. Understanding the mechanisms through which the cells of the immune system recognize MTB can be an important step in designing novel therapeutic approaches, as well as improving the limited success of current vaccination strategies. A great challenge in chronic disease is to understand the complexities, mechanisms, and consequences of host interactions with pathogens. Innate immune responses along with the involvement of distinct inflammatory mediators and cells play an important role in the host defense against the MTB. Several classes of pattern recognition receptors (PRRs) are involved in the recognition of MTB including Toll-Like Receptors (TLRs), C-type lectin receptors (CLRs) and Nod-like receptors (NLRs) linked to inflammasome activation. Among the TLR family, TLR1, TLR2, TLR4, and TLR9 and their down-stream signaling proteins play critical roles in the initiation of the immune response in the pathogenesis of TB. The inflammasome pathway is associated with the coordinated release of cytokines such as IL-1β and IL-18 which also play a role in the pathogenesis of TB. Understanding the cross-talk between these signaling pathways will impact on the design of novel therapeutic strategies and in the development of vaccines and immunotherapy regimes. Abnormalities in PRR signaling pathways regulated by TB will affect disease pathogenesis and need to be elucidated. In this review we provide an update on PRR signaling during M. tuberculosis infection and indicate how greater knowledge of these pathways may lead to new therapeutic opportunities

Secretome of mesenchymal stem cells and its impact on Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible loss of lung function that stem from two mechanisms, inflammation and senescence. Crosstalk between these two mechanisms accelerate the development of COPD, thus targeting these two pathways may offer benefits in the treatment of COPD. Growing amount of evidence have shown that mesenchymal stem cells as a promising candidate for the treatment of COPD. Over the years, many studies conducted to decipher the therapeutic effect of MSC in COPD and the mechanisms involve, in the hope of utilizing these cells as new therapeutic strategy for COPD. However, the cell-based therapy by using the MSC presented with many obstacles including low engraftment at the site of injury, the risk of microvascular occlusion, unwanted differentiation, and also the risk of malignant transformation. Recently, recently researchers begin to look at the possibility of using MSC derived extracellular vesicles as an alternative to MSC. Here we review the effect of MSC and MSC derived EV in modulating inflammation, and senescence in COPD. We also review current treatment and the side effect in COPD, and senolytic drugs, a new therapeutic strategy targeting the senescent cells