Dexmedetomidine protects against cisplatin-induced acute kidney injury in mice through regulating apoptosis and inflammation

Objective and design

Cisplatin-based chemotherapy has been widely used in the perioperative period of cancer surgery, which exacerbates the risk of renal injury. In this study, we examined whether dexmedetomidine (DEX), a commonly used anesthetic adjuvant, shows a protective effect against cisplatin-induced acute kidney injury.

Materials

Acute kidney injury in mice was induced by cisplatin.

Treatments

Mice were administered with DEX 25 μg/kg or atipamezole 250 μg/kg (once a day, for 3 days) after cisplatin treatment.

Methods

The renal function and tubular damage score were evaluated at 72 h following cisplatin administration. Apoptotic tubular cells were detected by TUNEL assay. Caspase-3, p53, Bax, F4/80⁺ macrophages, CD3⁺ T cells, and NF-κB were examined by immunohistochemistry staining or Western blot. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1 in kidney were measured using real-time polymerase chain reaction.

Results

DEX treatment preserved renal function and reduced tubular damage score of mice after cisplatin administration. Mice treated with DEX exhibited less apoptotic tubular cells in response to cisplatin insult, which was associated with decreased Bax and reduced activation of p53 and caspase-3. DEX suppressed the infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was involved in the inhibition of NF-κB activation and decreased expression of TNF-α, IL-1β, IL-6, and MCP-1. Furthermore, we showed that the renoprotective effect conferred by DEX may be related to α₂ adrenoceptor-dependent pathway.

Conclusion

We demonstrate that DEX protects the kidney against cisplatin-induced AKI by the regulation of apoptosis and inflammatory response.

     

Role of immune activation in CD4<Superscript>+</Superscript> T-cell depletion in HIV-1 infected Indian patients

Objectives

The correlation of immune activation with CD4⁺ depletion and HIV-1 disease progression has been evidenced by several studies involving mainly clade B virus. However, this needs to be investigated in developing countries such as India predominately infected with clade C virus.

Materials and methods

In a cross-sectional study of 68 antiretroviral treatment naïve, HIV-1 infected Indian patients, we studied the association between CD4⁺ T cells, plasma HIV-1 RNA levels, and immune activation markers using unadjusted and adjusted correlative analyses.

Results

Significant negative correlations of higher magnitude were observed between the CD4⁺ T cell percentages and plasma HIV-1 RNA levels in the study population when adjusted for the effects of immune activation markers. However, the negative association of CD4⁺ T cells with immune activation markers remained unaffected when controlled for the effects of plasma HIV-1 RNA levels.

Conclusions

Our results support the important role of immune activation in CD4⁺ T cell depletion and disease progression during untreated HIV-1 infection.

     

Expansion of CD11b<Superscript>+</Superscript>Ly6G<Superscript>high</Superscript> and CD11b<Superscript>+</Superscript>CD49d<Superscript>+</Superscript> myeloid cells with suppressive potential in mice with chronic inflammation and light-at-night-induced circadian disruption

Objective

Myeloid-derived suppressor cells (MDSCs) are important negative regulators of immune processes in cancer and other pathological conditions. We suggested that MDSCs play a key role in pathogenesis of chronic inflammation, which precedes and, to a certain extent, induces carcinogenesis. The present study aimed at investigation of MDSCs arising during chronic inflammation and light-at-night (LN)-induced stress, which is shown to accelerate chronic diseases.

Subjects

67 CD-1 mice and in vitro MDSC cultures.

Treatment

Adjuvant arthritis was induced by a subdermal injection of complete Freund’s adjuvant. LN was induced by illumination of 750 lx at night.

Methods

Flow cytometry for evaluation of cell phenotypes and MTT standard test for cell proliferation were used.

Results

Increased levels of splenic CD11b⁺Ly6G^high and CD11b⁺CD49d⁺ myeloid cells possessing suppressive potential in mice with adjuvant arthritis are shown. LN amplifies the process of CD11b⁺Ly6G^high expansion in mice with adjuvant arthritis. Expression of CD62L and CD195 is elevated on the myeloid cells during exposure to LN.

Conclusions

Our study raises the possibility that CD11b⁺Ly6G^high and CD11b⁺CD49d⁺ MDSCs play an important role in the induction of immunosuppressive environment typical for chronic inflammation. Also, LN can affect immune responses during chronic inflammation through recruitment of MDSCs from the bone marrow.

     

Location and gene-specific effects of methylprednisolone acetate on mitigating IL1β-induced inflammation in mature ovine explant knee tissue

Objective and design

To determine the ability of methylprednisolone acetate (MPA) to influence interleukin 1β (IL1β)-induced gene expression in ovine knee joint tissues.

Material or subjects

Ovine articular cartilage, synovium, and infrapatellar fat pad (IPFP) explants.

Treatment

Explants were treated with 10^?3 M or 10^?4 M MPA.

Methods

Explant treatment groups: (1) control (DMEM); (2) inflammation (IL1β); (3) IL1β + 10^?3 M MPA; or (4) IL1β + 10^?4 M MPA. Cell viability was assessed pre- and post-treatment. Expression of mRNA levels for inflammatory, degradative, anabolic, innate immunity, and adipose-related molecules was quantified via qPCR, and analyzed via the comparative C _T method.

Results

Except for IL8 in a subset of cartilage locations, matrix metalloproteinases (MMPs) were the only genes consistently affected by MPA. MPA mitigated IL1β-induced MMP3 expression levels in all regions of the articular cartilage, and in the synovium and IPFP, while MMP1 mRNA expression levels were significantly decreased with MPA after IL1β in the tibial plateau and synovium, but paradoxical increases in the IPFP. MMP13 mRNA expression levels exhibited significant decreases with MPA after IL1β in the femoral condyles, tibial plateau, synovium, and IPFP.

Conclusions

MPA treatment suppressed IL1β-induced mRNA levels for MMPs in articular cartilage, synovium, and IPFP and was found to be tissue-, location-, and gene-specific.

     

Varied sensitivity to therapy of HIV-1 strains in CD4<Superscript>+</Superscript> lymphocyte sub-populations upon ART initiation

Background

Although antiretroviral therapy (ART) has proven its success against HIV-1, the long lifespan of infected cells and viral latency prevent eradication. In this study we analyzed the sensitivity to ART of HIV-1 strains in naïve, central memory and effector memory CD4⁺ lymphocyte subsets.

Methods

From five patients cellular HIV-1 infection levels were quantified before and after initiation of therapy (2-5 weeks). Through sequencing the C2V3 region of the HIV-1 gp120 envelope, we studied the effect of short-term therapy on virus variants derived from naïve, central memory and effector memory CD4⁺ lymphocyte subsets.

Results

During short-term ART, HIV-1 infection levels declined in all lymphocyte subsets but not as much as RNA levels in serum. Virus diversity in the naïve and central memory lymphocyte populations remained unchanged, whilst diversity decreased in serum and the effector memory lymphocytes. ART differentially affected the virus populations co-circulating in one individual harboring a dual HIV-1 infection. Changes in V3 charge were found in all individuals after ART initiation with increases within the effector memory subset and decreases found in the naïve cell population.

Conclusions

During early ART virus diversity is affected mainly in the serum and effector memory cell compartments. Differential alterations in V3 charge were observed between effector memory and naïve populations. While certain cell populations can be targeted preferentially during early ART, some virus strains demonstrate varied sensitivity to therapy, as shown from studying two strains within a dual HIV-1 infected individual.

     

Greater frequency of CD5-negative CD8<Superscript>+</Superscript> T cells against human immunodeficiency virus type 1 than other viruses is consistent with adaptation to antigenic variation

Background

The CD5 protein antagonizes phosphorylation events downstream of T cell receptor (TCR) engagement to decrease T cell responsiveness. CD5-negative T cell clones respond preferentially over their CD5⁺ counterparts against cells with low human histocompatibility-linked leukocyte antigen (HLA) levels. In human immunodeficiency virus type 1 (HIV-1) infection, CD5^-CD8⁺ T cells increase in prevalence with disease progression.

Methods

To investigate potential causes of this expansion of CD5^-CD8⁺ T cells in HIV-1 infection, we compared CD5 expression on CD8⁺ T cells reactive against HIV-1 peptides, common viral peptides and a self peptide that together span a broad range of TCR avidities in the context of the common HLA-A2 class I restriction molecule. Following stimulation, CD5 expression on peptide-specific CD8⁺ T cells was assessed by flow cytometry.

Results

In healthy controls, there was no significant difference in the CD5⁺ percentage of CD8⁺ T cells specific for common viral peptides, but a lower percentage of those responding against a common self peptide expressed CD5. The same relationship occurred in HIV-infected individuals, however, a lower percentage of HIV peptide-specific CD8⁺ T cells than other viral peptide-specific CD8⁺ T cells expressed CD5. In terms of overall CD5 expression level at the peptide-specific responder population level, HIV-specific CD8⁺ T cells resembled those responsive against the self peptide, despite much higher avidity TCR/HLA/peptide interactions.

Conclusions

This deficit in CD5 expression selective for HIV-specific CD8⁺ T cells is consistent with in vivo adaptation to low avidity HIV peptide variants and has potential consequences for CD8⁺ T cell expansion, cross-reactivity and autoreactivity.

     

Clinical and Immunological Characterization of ICF Syndrome in Japan

Objective

Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare autosomal recessive primary immunodeficiency. Hypogammaglobulinemia is a major manifestation of ICF syndrome, but immunoglobulin replacement therapy does not seem to be effective for some ICF patients. Therefore, we aimed to reassess the immunological characteristics of this syndrome.

Methods

Eleven Japanese patients with ICF syndrome were enrolled. We performed whole-exome sequencing in four cases and homozygosity mapping using SNP analysis in two. We evaluated their clinical manifestations and immunological status.

Results

We newly diagnosed six ICF patients who had tentatively been diagnosed with common variable immunodeficiency. We identified two novel mutations in the DNMT3B gene and one novel mutation in the ZBTB24 gene. All patients showed low serum IgG and/or IgG₂ levels and were treated by periodic immunoglobulin replacement therapy. Three of the six patients showed worse results of the mitogen-induced lymphocyte proliferation test. Analyses of lymphocyte subpopulations revealed that CD19⁺CD27⁺ memory B cells were low in seven of nine patients, CD3⁺ T cells were low in three patients, CD4/8 ratio was inverted in five patients, CD31⁺ recent thymic emigrant cells were low in two patients, and CD19⁺ B cells were low in four patients compared with those in the normal controls. ICF2 patients showed lower proportions of CD19⁺ B cells and CD16⁺56⁺ NK cells and significantly higher proportions of CD3⁺ T cells than ICF1 patients. T cell receptor excision circles were undetectable in two patients. Despite being treated by immunoglobulin replacement therapy, three patients died of influenza virus, fatal viral infection with persistent Epstein–Barr virus infection, or JC virus infection. One of three dead patients showed normal intelligence with mild facial anomaly. Two patients presented with autoimmune or inflammatory manifestations. Infectious episodes decreased in three patients who were started on trimethoprim–sulfamethoxazole and/or antifungal drugs in addition to immunoglobulin replacement therapy. These patients might have suffered from T cell immunodeficiency.

Conclusion

These results indicate that patients with ICF syndrome have a phenotype of combined immunodeficiency. Thus, to achieve a better prognosis, these patients should be treated as having combined immunodeficiency in addition to receiving immunoglobulin replacement therapy.

     

Lipocalin 2 contributes to brain iron dysregulation but does not affect cognition,plaque load,and glial activation in the J20 Alzheimer mouse model

Background

Lipocalin 2 (Lcn2) is an acute-phase protein implicated in multiple neurodegenerative conditions. Interestingly, both neuroprotective and neurodegenerative effects have been described for Lcn2. Increased Lcn2 levels were found in human post-mortem Alzheimer (AD) brain tissue, and in vitro studies indicated that Lcn2 aggravates amyloid-β-induced toxicity. However, the role of Lcn2 has not been studied in an in vivo AD model. Therefore, in the current study, the effects of Lcn2 were studied in the J20 mouse model of AD.

Methods

J20 mice and Lcn2-deficient J20 (J20xLcn2 KO) mice were compared at the behavioral and neuropathological level.

Results

J20xLcn2 KO and J20 mice presented equally strong AD-like behavioral changes, cognitive impairment, plaque load, and glial activation. Interestingly, hippocampal iron accumulation was significantly decreased in J20xLcn2 KO mice as compared to J20 mice.

Conclusions

Lcn2 contributes to AD-like brain iron dysregulation, and future research should further explore the importance of Lcn2 in AD.

     

IL-33 signalling in liver immune cells enhances drug-induced liver injury and inflammation

Objective and design

The aim of this study was to investigate the contribution of IL-33/ST2 axis in the onset and progression of acute liver injury using a mice model of drug-induced liver injury (DILI).

Material and treatments

DILI was induced by overdose administration of acetaminophen (APAP) by oral gavage in wild-type BALB/c, ST2-deficient mice and in different bone marrow chimeras. Neutrophils were depleted by anti-Ly6G and macrophages with clodronate liposomes (CLL).

Methods

Blood and liver were collected for biochemical, immunologic and genetic analyses. Mice were imaged by confocal intravital microscopy and liver non-parenchymal cells and hepatocytes were isolated for flow cytometry, genetic and immunofluorescence studies.

Results

Acetaminophen overdose caused a massive necrosis and accumulation of immune cells within the liver, concomitantly with IL-33 and chemokine release. Liver non-parenchymal cells were the major sensors for IL-33, and amongst them, neutrophils were the major players in amplification of the inflammatory response triggered by IL-33/ST2 signalling pathway.

Conclusion

Blockage of IL-33/ST2 axis reduces APAP-mediated organ injury by dampening liver chemokine release and activation of resident and infiltrating liver non-parenchymal cells.

     

Passive administration of purified secretory IgA from human colostrum induces protection against <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> in a murine model of progressive pulmonary infection

Background

Immunoglobulin A is the most abundant isotype in secretions from mucosal surfaces of the gastrointestinal, respiratory and genitourinary tracts and in external secretions such as colostrum, breast milk, tears and saliva. The high concentration of human secretory IgA (hsIgA) in human colostrum strongly suggests that it should play an important role in the passive immune protection against gastrointestinal and respiratory infections.

Materials and methods

Human secretory IgA was purified from colostrum. The reactivity of hsIgA against mycobacterial antigens and its protective capacity against mycobacterial infection was evaluated.

Results

The passive administration of hsIgA reduces the pneumonic area before challenge with M. tuberculosis. The intratracheal administration of M. tuberculosis preincubated with hsIgA to mice greatly reduced the bacterial load in the lungs and diminished lung tissue injury.

Conclusions

HsIgA purified from colostrum protects against M. tuberculosis infection in an experimental mouse model.

     

Regulation of the NLRP3 inflammasome in <Emphasis Type="Italic">Porphyromonas gingivalis</Emphasis>-accelerated periodontal disease

Objective

Porphyromonas gingivalis is involved in the pathogenesis of chronic inflammatory periodontal disease. Recent studies have suggested that the NLRP3 inflammasome plays an important role in the development of chronic inflammation. We investigated a possible association between the inflammasome in gingival inflammation and bone loss induced by P. gingivalis infection using NLRP3-deficient mice.

Methods

Wild-type and NLRP3-deficient mice were injected orally with P. gingivalis. We assessed alveolar bone loss, expression of pro-interleukin (IL)-1β, pro-IL-18, receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) in gingival tissue, as well as IL-1β, IL-18, and IL-6 production and caspase-1 activity in peritoneal macrophages.

Results

Porphyromonas gingivalis challenge significantly increased alveolar bone loss; gingival gene expression of pro-IL-1β, pro-IL-18, and RANKL; production of IL-1β, IL-18, and IL-6; and caspase-1 activity in peritoneal macrophages of wild-type mice, but did not affect NLRP3-deficient mice. Meanwhile, OPG mRNA expression in gingival tissue and peritoneal IL-6 production were significantly higher in NLRP3-knockout mice.

Conclusions

Porphyromonas gingivalis activated innate immune cells via the NLRP3 inflammasome. These results suggest that the NLRP3 inflammasome, followed by a response from the IL-1 family, is critical in periodontal disease induced by wild-type P. gingivalis challenge via sustained inflammation.

     

γδT cells but not αβT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice

Background

Infection and sepsis are associated with brain white matter injury in preterm infants and the subsequent development of cerebral palsy.

Methods

In the present study, we used a neonatal mouse sepsis-induced white matter injury model to determine the contribution of different T cell subsets (αβT cells and γδT cells) to white matter injury and consequent behavioral changes. C57BL/6J wild-type (WT), T cell receptor (TCR) δ-deficient (Tcrd ^?/?, lacking γδT cells), and TCRα-deficient (Tcra ^?/?, lacking αβT cells) mice were administered with lipopolysaccharide (LPS) at postnatal day (PND) 2. Brain myelination was examined at PNDs 12, 26, and 60. Motor function and anxiety-like behavior were evaluated at PND 26 or 30 using DigiGait analysis and an elevated plus maze.

Results

White matter development was normal in Tcrd ^?/? and Tcrα ^?/? compared to WT mice. LPS exposure induced reductions in white matter tissue volume in WT and Tcrα ^?/? mice, but not in the Tcrd ^?/? mice, compared with the saline-treated groups. Neither LPS administration nor the T cell deficiency affected anxiety behavior in these mice as determined with the elevated plus maze. DigiGait analysis revealed motor function deficiency after LPS-induced sepsis in both WT and Tcrα ^?/? mice, but no such effect was observed in Tcrd ^?/? mice.

Conclusions

Our results suggest that γδT cells but not αβT cells contribute to sepsis-induced white matter injury and subsequent motor function abnormalities in early life. Modulating the activity of γδT cells in the early stages of preterm white matter injury might represent a novel therapeutic strategy for the treatment of perinatal brain injury.

     

Prevention of allergic airway hyperresponsiveness and remodeling in mice by <Emphasis Type="Italic">Astragaliradix</Emphasis> Antiasthmatic decoction

Background

Astragali radix Antiasthmatic Decoction (AAD), a traditional Chinese medication, is found effective in treating allergic diseases and chronic cough. The purpose of this study is to determine whether this medication could suppress allergen-induced airway hyperresponsiveness (AHR) and remodeling in mice, and its possible mechanisms.

Methods

A mouse model of chronic asthma was used to investigate the effects of AAD on the airway lesions. Mice were sensitized and challenged with ovalbumin (OVA), and the extent of AHR and airway remodeling were characterized. Cells and cytokines in the bronchoalveolar lavage fluid (BALF) were examined.

Results

AAD treatment effectively decreased OVA-induced AHR, eosinophilic airway inflammation, and collagen deposition around the airway. It significantly reduced the levels of IL-13 and TGF-β1, but exerted inconsiderable effect on INF-γ and IL-10.

Conclusions

AAD greatly improves the symptoms of allergic airway remodeling probably through inhibition of Th2 cytokines and TGF-β1.

     

Daphnetin reduces endotoxin lethality in mice and decreases LPS-induced inflammation in Raw264.7 cells via suppressing JAK/STATs activation and ROS production

Objective

Here, we used various approaches to investigate the suppressive role of daphnetin in LPS-induced inflammatory response, with the goal to understand the underlining molecular mechanism by which daphnetin regulated these processes.

Methods

We examined the survival rate and the lung injury in the mice model of LPS-induced endotoxemia. The production of pro-inflammatory factors including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), IL-6, nitric oxide (NO), and prostaglandin E2 (PGE2) was measured by ELISA and nitrite analysis, respectively. The expression of inducible NO synthase (iNOS), cyclooxygenase 2 (COX-2), and the activation of signaling molecules was determined by immunoblotting. The production of reactive oxygen species (ROS) was measured by the ROS assay.

Results

In vivo study showed that daphnetin enhanced the survival rate and reduced the lung injury in mice with LPS-induced endotoxemia. Both in vivo and in vitro study showed that daphnetin prevented the production of pro-inflammatory factors including TNF-α, IL-1β, IL-6, NO, and PGE2 after LPS challenge. In Raw264.7 cells, we found that daphnetin reduced LPS-induced expression of iNOS and COX-2, and suppressed LPS-induced ROS production. In addition, we found that daphnetin suppressed the activation of JAK/STATs pathway and inhibited the nucleus import of STAT1 and STAT3.

Conclusions

Here, our results indicate that daphnetin shows anti-inflammatory properties, at least in part, through suppressing LPS-induced activation of JAK/STATs cascades and ROS production.

     

The host control of a clinical isolate strain of <Emphasis Type="Italic">P. aeruginosa</Emphasis> infection is independent of Nod-1 but depends on MyD88

Objective and design

The objective of this study was to investigate the role of Nod1 in the recruitment of neutrophils into the infection site and in the establishment of the inflammatory response elicited by a clinical isolate strain of P. aeruginosa in vivo, while comparing it to the well-established role of MyD88 in this process.

Subjects

Wild-type, Nod1^?/? and MyD88^?/? mice, all with a C57Bl/6 background.

Methods

Mice were intranasally infected with Pseudomonas aeruginosa DZ605. Bronchoalveolar lavage and blood were harvested 6 or 20 h post-infection for evaluating bacterial load, chemokine levels and neutrophil migration. Survival post-infection was also observed.

Results

We show here that wild-type and Nod1^?/? mice induce similar lung chemokine levels, neutrophil recruitment, and bacterial load, thus leading to equal survival rates upon P. aeruginosa pulmonary infection. Furthermore, we confirmed the essential role of MyD88-dependent signalling in recruiting neutrophils and controlling P. aeruginosa-induced pulmonary infection.

Conclusion

The results suggest that in contrast to MyD88, under our experimental conditions, the absence of Nod1 does not impair the recruitment of neutrophils in response to P. aeruginosa DZ605.

     

Effects of COX1-2/5-LOX blockade in Alzheimer transgenic 3xTg-AD mice

Objective and design

Alzheimer’s disease (AD) is associated with amyloid plaques (Aβ) and hyperphosphorylated tau protein tangles in the brain. We investigated the possible neuroprotective role of flavocoxid, a dual inhibitor of cyclooxygenases-1/2 (COX-1/2) and 5-Lipoxygenase (5-LOX), in triple-transgenic (3xTg-AD) mice.

Subjects

Mice were 3 months at the beginning of the study.

Treatment

Animals received once daily for 3-month saline solution or flavocoxid (20 mg/kg/ip).

Methods

Morris water maze was used to assess learning and memory. Histology was performed to evidence Aβ plaques and neuronal loss, while inflammatory proteins were determined by western blot analysis.

Results

Saline-treated 3xTg-AD mice showed an impairment in spatial learning and memory (assessed at 6 months of age), and increased expression of inflammatory and apoptotic molecules. Treatment of 3xTg-AD mice with flavocoxid reduced: (1) learning and memory loss; (2) the increased eicosanoid production and the phosphorylation level of amyloid precursor protein (APP-pThr668), Aβ 1–42, p-tau (pThr181), pERK, and the activation of the NLRP3 inflammasome; (3) Aβ plaques; and (4) neuronal loss, compared to saline-treated animals.

Conclusions

Pharmacological blockade of both COX-1/2 and 5-LOX was able to counteract the progression of AD by targeting pathophysiological mechanisms up- and downstream of Aβ and tau.

     

<Emphasis Type="Italic">Helicobacter bilis</Emphasis>-Associated Suppurative Cholangitis in a Patient with X-Linked Agammaglobulinemia

?

Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases.

Purpose

We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis.

Methods

16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis.

Results

Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin.

Conclusion

In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.

     

Ouabain attenuates ovalbumin-induced airway inflammation

Purpose

Ouabain, an Na⁺/K⁺-ATPase inhibitor hormone, presents immunomodulatory actions, including anti-inflammatory effect on acute inflammation models.

Methods

In the present study, the effect of ouabain in a model of allergic airway inflammation induced by ovalbumin (OVA) was assessed.

Results

Initially, it was observed that ouabain treatment inhibited cellular migration induced by OVA on bronchoalveolar lavage fluid (BALF), mostly granulocytes, without modulating macrophage migration. In addition, it was observed, by flow cytometry, that ouabain reduces CD3^high lymphocytes cells on BALF. Furthermore, treatment with ouabain decreased IL-4 and IL-13 levels on BALF. Ouabain also promoted pulmonary histological alterations, including decreased cell migration into peribronchiolar and perivascular areas, and reduced mucus production in bronchioles regions observed through hematoxylin–eosin (HE) and by periodic acid-Schiff stain, respectively. Allergic airway inflammation is characterized by high OVA-specific IgE serum titer. This parameter was also reduced by the treatment with ouabain.

Conclusions

Therefore, our data demonstrate that ouabain negatively modulates allergic airway inflammation induced by OVA.