Oral feeding of Lactobacillus bulgaricus N45.10 inhibits the lung inflammation and airway remodeling in murine allergic asthma: Relevance to the Th1/Th2 cytokines and STAT6/T-bet.

Asthma is a chronic disease with impacts on public health. It affects the airways causing pulmonary inflammation mediated by CD4 T cells type Th2, eosinophilia, mucus hypersecretion, and elevated IgE. The unbalance between cytokines and transcription factors is an important feature in asthma. Probiotics has gaining highlight as a therapy for chronic diseases. Thus, we investigate the Lactobacillus bulgaricus (Lb) effect in murine allergic asthma. BALB/c-mice were sensitized to ovalbumin (OA) on days 0 and 7 and were challenged from day 14-28 with OA. Mice received Lb seven days prior to sensitization and it was kept until day 28. The Lb attenuated the eosinophils infiltration, mucus and collagen secretion, IgE production, pro-inflammatory cytokines, TLR4 expression, GATA3, STAT6 and RORγt in lung. Otherwise, Lb increased the anti-inflammatory cytokines, the T-bet and foxp3. Finally, Lb attenuated the allergic asthma-induced inflammation and airway remodeling by interfering on Th1/Th2 cytokines and STAT6/T-bet transcription factors.

Beneficial effect of low-level laser therapy in acute lung injury after i-I/R is dependent on the secretion of IL-10 and independent of the TLR/MyD88 signaling.

The use of low-level laser for lung inflammation treatment has been evidenced in animal studies as well as clinical trials. The laser action mechanism seems to involve downregulation of neutrophil chemoattractants and transcription factors. Innate immune responses against microorganisms may be mediated by toll-like receptors (TLR). Intestinal ischemia and reperfusion (i-I/R) lead to bacterial product translocation, such as endotoxin, which consequently activates TLRs leading to intestinal and lung inflammation after gut trauma. Thus, the target of this study was to investigate the role of TLR activation in the laser (660 nm, 30 mW, 67.5 J/cm2, 0.375 mW/cm2, 5.4 J, 180 s, and spot size with 0.08 cm2) effect applied in contact with the skin on axillary lymph node in lung inflammation induced by i-I/R through a signaling adaptor protein known as myeloid differentiation factor 88 (MyD88). It is a quantitative, experimental, and laboratory research using the C57Bl/6 and MyD88-/- mice (n = 6 mice for experimental group). Statistical differences were evaluated by ANOVA and the Tukey-Kramer multiple comparisons test to determine differences among groups. In order to understand how the absence of MyD88 can interfere in the laser effect on lung inflammation, MyD88-/- mice were treated or not with laser and subjected to occlusion of the superior mesenteric artery (45 min) followed by intestinal reperfusion (4 h). In summary, the laser decreased the MPO activity and the lung vascular permeability, thickened the alveolar septa, reduced both the edema and the alveolar hemorrhage, as well as significantly decreased neutrophils infiltration in MyD88-deficient mice as well in wild-type mice. It noted a downregulation in chemokine IL-8 production as well as a cytokine IL-10 upregulation in these animals. The results also evidenced that in absence of IL-10, the laser effect is reversed. Based on these results, we suggest that the beneficial effect of laser in acute lung injury after i-I/R is dependent on the secretion of IL-10 and independent of the TLR/MyD88 signaling.

Oral feeding with probiotic Lactobacillus rhamnosus attenuates cigarette smoke-induced COPD in C57Bl/6 mice: Relevance to inflammatory markers in human bronchial epithelial cells.

COPD is a prevalent lung disease with significant impacts on public health. Affected airways exhibit pulmonary neutrophilia and consequent secretion of pro-inflammatory cytokines and proteases, which result in lung emphysema. Probiotics act as nonspecific modulators of the innate immune system that improve several inflammatory responses. To investigate the effect of Lactobacillus rhamnosus (Lr) on cigarette smoke (CS)-induced COPD C57Bl/6 mice were treated with Lr during the week before COPD induction and three times/week until euthanasia. For in vitro assays, murine bronchial epithelial cells as well as human bronchial epithelial cells exposed to cigarette smoke extract during 24 hours were treated with Lr 1 hour before CSE addition. Lr treatment attenuated the inflammatory response both in the airways and lung parenchyma, reducing inflammatory cells infiltration and the production of pro-inflammatory cytokines and chemokines. Also, Lr-treated mice presented with lower metalloproteases in lung tissue and lung remodeling. In parallel to the reduction in the expression of TLR2, TLR4, TLR9, STAT3, and NF-κB in lung tissue, Lr increased the levels of IL-10 as well as SOCS3 and TIMP1/2, indicating the induction of an anti-inflammatory environment. Similarly, murine bronchial epithelial cells as well as human bronchial epithelial cells (BEAS) exposed to CSE produced pro-inflammatory cytokines and chemokines, which were inhibited by Lr treatment in association with the production of anti-inflammatory molecules. Moreover, the presence of Lr also modulated the expression of COPD-associated transcription found into BALF of COPD mice group, i.e., Lr downregulated expression of NF-κB and STAT3, and inversely upregulated increased expression of SOCS3. Thus, our findings indicate that Lr modulates the balance between pro- and anti-inflammatory cytokines in human bronchial epithelial cells upon CS exposure and it can be a useful tool to improve the lung inflammatory response associated with COPD.

Proteome of Rhipicephalus sanguineus tick saliva induced by the secretagogues pilocarpine and dopamine.

One dimensional gel electrophoresis was used to separate proteins from the saliva of Rhipicephalus sanguineus female ticks fed on rabbits. Gel slices were subjected to tryptic digestion and analyzed by reversed-phase HPLC followed by MS/MS analysis. The data were compared to a database of salivary proteins of the same tick and to the predicted proteins of the host. Saliva was obtained by either pilocarpine or dopamine stimulation of partially fed ticks. Electrophoretic separations of both yielded products that were identified by mass spectrometry, although the pilocarpine-derived sample was of much better quality. The majority of identified proteins were of rabbit origin, indicating the recycling of the host proteins in the tick saliva, including hemoglobin, albumin, haptoglobin, transferring, and a plasma serpin. The few proteins found that were previously associated with parasitism and blood feeding include 2 glycine-rich, cement-like proteins, 2 lipocalins, and a thyropin protease inhibitor. Among other of the 19 tick proteins identified, albeit with undefined roles, were SPARC and cyclophilin A. This catalog provides a resource that can be mined for secreted molecules that play a role in tick-host interactions.