Rationale: Nuclear factor (NF)-kB is a prominent proinflammatory transcription factor that plays a critical role in allergic airway disease. Previous studies demonstrated that inhibition of NF-kB in airway epithelium causes attenuation of allergic inflammation. Objectives: We sought to determine if selective activation of NF-kB within the airway epithelium in the absence of other agonists is sufficient to cause allergic airway disease. Methods: A transgenic mouse expressing a doxycycline (Dox)-inducible, constitutively active (CA) version of inhibitor of kB (IkB) kinase-b (IKKb) under transcriptional control of the rat CC10 promoter, was generated. Measurements and Main Results: After administration of Dox, expression of the CA-IKKb transgene induced the nuclear translocation of RelA in airway epithelium. IKKb-triggered activation of NF-kB led to an increased content of neutrophils and lymphocytes, and concomitant production of proinflammatory mediators, responses that were not observed in transgenic mice not receiving Dox, or in transgenenegative littermate control animals fed Dox. Unexpectedly, expression of the IKKb transgene in airway epithelium was sufficient to cause airway hyperresponsiveness and smooth muscle thickening in absence of an antigen sensitization and challenge regimen, the presence of eosinophils, or the induction of mucus metaplasia.Conclusions: These findings demonstrate that selective activation NFkB in airway epithelium is sufficient to induce airway hyperresponsiveness and smooth muscle thickening, which are both critical features of allergic airway disease.

Mucus hyperproduction in asthma results from Th2-induced airway inflammation. Controversy exists about the precise mechanism of this Th2 effect. Although we showed that mucus can be induced by Th2 cells in the absence of interleukin (IL)-4, IL-5, eosinophils, and mast cells, but not without IL-4Ralpha signaling, others demonstrated that IL-4 and IL-9 can directly stimulate airway epithelial mucus. Using a system in which in vitro-generated T cell receptor transgenic Th2 cells are transferred into recipient mice and activated in the respiratory tract with inhaled antigen, we now show that CD4 Th cells can stimulate mucus only through a common, IL-13-mediated pathway. All Th cytokines depend on IL-13 for this effect and IL-13 acts, not through intermediate inflammatory cells, but on structural cells within the lung, likely the airway epithelium itself. The potency of IL-13 is shown, requiring its complete blockade for a significant reduction in mucus production. We show that mucus induction by Th2 cells does not require nuclear factor-kappaB, unlike mucins induced by gram-negative infection. These studies define in vivo pathways that lead to mucus induction and indicate that, whereas IL-13 mediates a dominant pathway for CD4 Th induced inflammation, other inflammatory stimuli activate the epithelium to produce mucus by different pathways.

Background Healthy vaginal microbiome is dominated by Lactobacilli, which constitute a strong line of defense against vaginal diseases like Bacterial vaginosis (BV). Bacterial Vaginosis is a polymicrobial disease characterized by gradual replacement of predominant population of Lactobacillus with anaerobic uropathogens such as Gardnerella vaginalis (GV), Prevotella and Mobiluncus spp. Due to antibiotic resistance in these pathogens, Lactobacillus spp. have been given attention in the prophylaxis and prevention of infections such as, urinary tract infections, genital infections and BV. Current study describes role of L. reuteri in reducing BV in a GV induced BV murine model. In addition, immunomodulatory effects of L. reuteri were assessed by analyzing gene expression of in ammatory and anti-in ammatory markers by real time PCR in vaginal tissue. Methods Study was divided into two parts. In phase 1, two groups of mice were intravaginally administered with L. reuteri and GV at a dose of 1 x 10 6 CFUml-1 and 5 x 10 5 CFUml-1 respectively and their colonization was con rmed by re-isolation of these strains in vaginal washes. In phase 2, prophylactic e cacy of L. reuteri in GV induced BV mice model were observed by considering clinical scoring, re-isolation frequency, bacterial load, change in epithelium of vaginal tissue and tissue in ammatory and anti-in ammatory markers. Results A signi cant reduction in clinical scores and re-isolation frequency was noticed in GV challenged pre-L. reuteri colonized animals (prophylactic group). On 10 th day, L. reuteri restricted the growth of GV