Rationale: Pro-inflammatory cytokines released during influenza infection is one of the major causes of lung injury. Detection of virus by pattern recognition receptors (PRRs) like toll like receptors (TLRs), and endoplasmic reticulum (ER) stress contributes to exacerbated release of cytokines following infection. Influenza A virus (IAV) – induced ER stress occurs due to rapid replication of viral RNPs and increased translational burden on the ER causing accumulation of unfolded proteins and activation of an adaptive response called the unfolded protein response (UPR). PKR-like kinase (PERK), one of the members of the UPR pathway plays a direct role in decreasing the translational burden. Phosphorylation of PERK (P-PERK) during UPR activation and its involvement in pro-inflammatory cytokine release is well established, but only in various models of sterile infection. Although a decrease in cytokine production was observed when P-PERK was inhibited in the above-mentioned studies, it is not clear if it was under transcriptional or translational regulation by P-PERK. Our objective is to determine the role of P-PERK in pro-inflammatory cytokine release during IAV infection. In addition, we will also determine the mode of regulation by which these cytokines are controlled and whether P-PERK can be targeted to prevent cytokine storm during IAV infection. Methods: Cell culture experiments to study ER-stress and cytokine release were studied in human bronchial epithelial cells (HBEC3KT) infected with IAV. Activation of UPR and PERK in IAV infected cells was confirmed by Western blots. Pro-inflammatory cytokines released under the control of P-PERK were identified using an inhibitor, GSK2606414 (PERKi) that inhibits PERK activation. Transcriptional and translational regulation was studied using qPCR and polysome profiling respectively. C57BL/6 mice were infected with 2000 EIU of IAV/PR8 intranasally and treated with varying concentrations of PERKi. Results: We found that PERK was phosphorylated 24 hours post infection and sustained until 48 hours post infection in HBEC3KT cells. These cells were treated with 5 M PERKi during infection showed significant decrease in PERK phosphorylation. Pro-inflammatory cytokines like IL6, IL8, CCL4 and CCL20 were significantly decreased in the supernatants following PERKi treatment. Both IL6 and CCL4 exhibited a decrease in translational efficiency following PERKi treatment. Conclusion: These results suggest PERK's involvement in overt cytokine release during IAV infection.

Nanotechnology has emerged as a transformative tool in reproductive research and therapy for both humans and livestock. In human medicine, nanomaterials are being explored for targeted drug delivery to treat infertility, enhance assisted reproductive technologies, and improve in vitro embryo production outcomes. These approaches hold significant potential to address infertility, which affects around 15% of couples worldwide. In the livestock sector, nanotechnology offers promising applications for boosting agricultural productivity by optimizing breeding outcomes, improving semen quality, and enabling precise genetic modifications for the production of genome-edited animals. This commentary explores the complex interplay of nanotoxicity, ethical challenges, and policy imperatives in the context of human and livestock reproductive research and therapy. By examining the mechanisms and risks of nanotoxicity, ethical dilemmas in clinical and agricultural settings, and the need for comprehensive regulatory frameworks, we aim to provide a roadmap for navigating this rapidly evolving field. The goal is to balance innovation with safety, ensuring that nanotechnology’s benefits are realized without compromising health, welfare, or public trust.

RATIONALE: During periods of stress or high protein synthesis, unfolded and misfolded proteins accumulate in the lumen of the endoplasmic reticulum (ER). In response, a series of pathways called the unfolded protein response (UPR) are activated to process unfolded proteins. Elevated ER stress and UPR signaling has been implicated in allergic asthma and is regulated by chaperone protein BiP, which, under homeostatic conditions, is bound to three UPR transducers: IRE1, PERK, and ATF6. UPR activation occurs when BiP dissociates from these transducers, however, the mechanism for dissociation in allergic airway disease is unknown. Mass spectrometry data from our allergic airway disease mouse model revealed a novel sulfenylation modification of BiP which was associated with enhanced UPR activation, and attenuation of mitochondrial ROS decreased BiP sulfenylation in allergen challenged mice, including decrease in inflammation and AHR. Yeast studies have shown that sulfenylation of the lone cysteine residue results in increased chaperone capability of BiP, however, the effect sulfenylation on BiP dissociation from the UPR transducers in mammalian system is unknown. Additionally, mammalian BiP has two cysteines and the effect of sulfenyation remains unknown. We hypothesize that sulfenylation of BiP results in BiP/IRE1 dissociation and elevated IRE1 activity which could provide a potential target for mitigating ER stress in allergic asthma. METHODS: HBEC3KT cells were dosed with 25ug/mL of HDM. Protein and RNA lysates were collected 6, 24, and 48hrs after HDM dose. Cells were transfected with 750ng of mutant BiP plasmids 24hrs prior to HDM treatment. UPR expression was measured using western blot and RT-qPCR. BiP sulfenylation was measured using DCP-Bio1 and neutravidin pulldown. Interaction between BiP and IRE1 was evaluated through immunoprecipitation. Mice were sensitized intranasally with 25ug HDM on days 1 and 7 then challenged on days 14-18. MitoQ was administered via intraperitoneal injection on days 17-19. Cytokine analysis was evaluated via ELISA.RESULTS: BiP sulfenylation is associated with increased activity of IRE1 and decreased association of BiP with IRE1 in response to HDM. BiP C41a mutant overexpression resulted in increased association with IRE1 and decreased IRE1 signaling. BiP C420a mutant overexpression resulted in the formation of a truncated product implying that C420 is crucial for BiP structure. In mice, MitoQ treatment decreased BiP sulfenylation, IRE1 activation, inflammation, and AHR. CONCLUSIONS: These findings provide evidence for a novel oxidative post translational modification involved in activation of the IRE1 pathway and can provide potential targets for treatment of allergic airway disease.

Goat semen cryopreservation plays a crucial role in the management and improvement of breeding programs, but it is accompanied by numerous challenges that hinder its success. The high cryo-sensitivity of goat sperm, particularly due to their lipid-rich membranes, makes them susceptible to damage during freezing and thawing processes. Additionally, the composition of seminal plasma, seasonal variations, and breed-specific differences further complicate semen preservation. This review highlights the key factors that influence the cryopreservation of goat semen, including the role of cryoprotectants, antioxidants, and the freezing-thawing protocols. Advances in techniques such as vitrification, freeze-drying, and the use of nanotechnology are discussed, as they offer promising solutions to improve post-thaw sperm quality. Furthermore, the application of bio- stimulants and novel extenders has shown potential in enhancing sperm survival and functionality. Despite the progress made, further improvements are necessary to address issues such as oxidative stress, cryodamage, and environmental factors. By addressing the challenges and limitations in the existing preservation methods, this article seeks to provide valuable insights for researchers, practitioners, and the broader livestock industry involved in goat breeding and reproduction.

Background and PurposeFibrotic lung remodelling after a respiratory viral infection represents a debilitating clinical sequela. Studying or managing viral-fibrotic sequela remains challenging, due to limited therapeutic options and lack of understanding of mechanisms. This study determined whether protein disulfide isomerase A3 (PDIA3) and secreted phosphoprotein 1 (SPP1), which are associated with pulmonary fibrosis, can promote influenza-induced lung fibrotic remodelling and whether inhibition of PDIA3 or SPP1 can resolve viral-mediated fibrotic remodelling.Experimental ApproachA retrospective analysis of TriNetX data sets was conducted. Serum from healthy controls and influenza A virus (IAV)-infected patients was analysed. An inhibitor of PDIA3, punicalagin, and a neutralizing antibody for SPP1 were administered in mice. Macrophage cells treated with macrophage colony-stimulating factor (M-CSF) were used as a cell culture model.Key ResultsThe TriNetX data set showed an increase in lung fibrosis and decline in lung function in flu-infected acute respiratory distress syndrome (ARDS) patients compared with non-ARDS patients. Serum samples revealed a significant increase in SPP1 and PDIA3 in influenza-infected patients. Lung PDIA3 and SPP1 expression increased following viral infection in mouse models. Punicalagin administration 2 weeks after IAV infection in mice caused a significant decrease in lung fibrosis and improved oxygen saturation. Administration of neutralizing SPP1 antibody decreased lung fibrosis. Inhibition of PDIA3 decreased SPP1secretion from macrophages, in association with diminished disulfide bonds in SPP1.Conclusion and ImplicationsThe PDIA3-SPP1 axis promotes post-influenza lung fibrosis in mice and that pharmacological inhibition of PDIA3 or SPP1 can treat virus-induced lung fibrotic sequela. image

Introduction: Direct laryngoscopy followed by intubation induces a stress response leading to haemodynamic changes that are often transient, unpredictable, and variable. Both dexmedetomidine and lignocaine have been used in nebulised form successfully to blunt haemodynamic stress response, but they have never been compared previously. Aim: To compare nebulised dexmedetomidine and nebulised lignocaine in blunting the haemodynamic response to laryngoscopy and endotracheal intubation. Materials and Methods: This randomised, double-blinded study was conducted on 135 patients with American Society of Anesthesiologists (ASA) physical Status I and II, aged 18 to 60 years, planned for surgery under general anaesthesia with endotracheal intubation. Patients were divided into three groups of 45 each using a computer-generated random number table. Patients in group D were nebulised with dexmedetomidine 1 μg/ kg, with lignocaine 1.5 mg/kg in group L, and with normal saline in group C. The primary objective was to compare nebulised dexmedetomidine and nebulised lignocaine in blunting the haemodynamic response to laryngoscopy and endotracheal intubation with respect to Heart Rate (HR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure, and Mean Arterial Pressure (MAP). The secondary objective was to study sideeffects associated with the use of nebulised dexmedetomidine and lignocaine. Results: The demographic profile was found to be comparable in all three groups. The mean age was 40.44±11.77 years, 40.04±12.33 years, and 42.89±11.57 years in group D, group L, and group C, respectively, with a p-value of 0.4. The rise in HR during intubation and at all later time points was found to be less in group D and group L compared to group C. Additionally, the rise in HR was found to be higher in group L compared to group D. Similarly, the attenuation effect on SBP and Diastolic Blood Pressure (DBP) was greater in group D patients. Conclusion: Both nebulised dexmedetomidine and lignocaine were effective in attenuating the pressor response during laryngoscopy and intubation, with dexmedetomidine being more effective than lignocaine without any adverse haemodynamic effects.

This study was aimed to decipher the inter-relationship peripheral hormones [Insulin-like growth hormone (IGF-1), testosterone and growth hormone] with body weight, body condition score and scrotal circumfermnce across age-groups in male buffalo. Male buffalo (n=20) of different age groups viz. Group 1 (0 to 8 months), 2 (9 to 16 months), 3 (17 to 24 months) and 4 (25 to 32 months) were selected and Blood was collected along with body weight, body condition score and scrotal circumference. Significant difference (P<0.05) in the body weight, body condition core and scrotal circumference was observed between the groups. Peripheral IGF-1 level increased with age, highest in Group 4 (202.4±9.36 ng/ml). Similarly, testosterone was different between Group 1, 2 and 4, highest in Group 4 (1.73±0.02 ng/ml). Growth hormone, differed (P<0.05) between Group 1 (3.65±0.50 ng/ml), Group 3 (3.65±0.50 ng/ml) and Group 4 (8.56±1.96 ng/ml). Postive correlation (P<0.05) between various parameters (body weight, body condition score and scrotal circumference, testosterone and growth hormone) was observed. In conclusion, this study reports the age-related variations and inter-relationships of peripheral hormones with body weight, body condition score and scrotal circumference in male buffalo.

Obesity is a risk factor for severe influenza, and asthma exacerbations caused by respiratory viral infections. We investigated mechanisms that increase the severity of airway disease related to influenza in obesity using cells derived from obese and lean individuals, and in vitro and in vivo models. Primary human nasal epithelial cells (pHNECs) derived from obese compared with lean individuals developed increased inflammation and injury in response to influenza A virus (IAV). Obese mice infected with influenza developed increased airway inflammation, lung injury and elastance, but had a decreased interferon response, compared with lean mice. Lung arachidonic acid (AA) levels increased in obese mice infected with IAV; arachidonic acid increased inflammatory cytokines and injury markers in response to IAV in human bronchial epithelial (HBE) cells. Obesity in mice, and AA in HBE cells, increased activation of p38 MAPK signaling following IAV infection; inhibiting this pathway attenuated inflammation, injury and tissue elastance responses, and improved survival. In summary, obesity increases disease severity in response to influenza infection through activation of the p38 MAPK pathway in response to altered arachidonic acid signaling.

Obesity is associated with severe, difficult-to-control asthma, and increased airway oxidative stress. Mitochondrial reactive oxygen species (mROS) are an important source of oxidative stress in asthma, leading us to hypothesize that targeting mROS in obese allergic asthma might be an effective treatment. Using a mouse model of house dust mite (HDM)-induced allergic airway disease in mice fed a low- (LFD) or high-fat diet (HFD), and the mitochondrial antioxidant MitoQuinone (MitoQ), we investigated the effects of obesity and ROS on HDM-induced airway inflammation, remodeling, and airway hyperresponsiveness (AHR). Obese allergic mice showed increased lung tissue eotaxin, airway tissue eosinophilia, and AHR compared with lean allergic mice. MitoQ reduced airway inflammation, remodeling, and hyperreactivity in both lean and obese allergic mice, and tissue eosinophilia in obese-allergic mice. Similar effects were observed with decyl triphosphonium (dTPP+), the hydrophobic cationic moiety of MitoQ lacking ubiquinone. HDM-induced oxidative sulfenylation of proteins was increased particularly in HFD mice. Although only MitoQ reduced sulfenylation of proteins involved in protein folding in the endoplasmic reticulum (ER), ER stress was attenuated by both MitoQ and dTPP+ suggesting the anti-allergic effects of MitoQ are mediated in part by effects of its hydrophobic dTPP+ moiety reducing ER stress. In summary, oxidative signaling is an important mediator of allergic airway disease. MitoQ, likely through reducing protein oxidation and affecting the UPR pathway, might be effective for the treatment of asthma and specific features of obese asthma.

Influenza (IAV) neuraminidase (NA) is a glycoprotein required for the viral exit from the cell. NA requires disulfide bonds for proper function. We have recently demonstrated that protein disulfide isomerase (PDI)A3 is required for oxidative folding of IAV hemagglutinin (HA), and viral propagation. However, it not known whether PDIs are required for NA maturation or if these interactions represent a putative target for the treatment of influenza infection. We sought to determine whether PDIA3 is required for disulfide bonds of NA, its activity, and propagation of the virus. Requirement of disulfides for NA oligomerization and activity were determined using biotin switch and redox assays in WT and PDIA3−/− in A549 cells. A PDI specific inhibitor (LOC14) was utilized to determine the requirement of PDIs in NA activity, IAV burden, and inflammatory response in A549 and primary mouse tracheal epithelial cells. Mice were treated with the inhibitor LOC14 and subsequently examined for IAV burden, NA activity, cytokine, and immune response. IAV-NA interacts with PDIA3 and this interaction is required for NA activity. PDIA3 ablation or inhibition decreased NA activity, viral burden, and inflammatory response in lung epithelial cells. LOC14 treatment significantly attenuated the influenza-induced inflammatory response in mice including the overall viral burden. These results provide evidence for PDIA3 inhibition suppressing NA activity, potentially providing a novel platform for host-targeted antiviral therapies.

A four year old Murrah buffalo at full term in second parity suffering from dystocia was presented to the Veterinary Clinical Complex and the fetal monster was delivered by caesarean section. The fetus was Dicephalic dibrachius dipus dicaudatus along with partial duplication of spine.

Sperm mitochondrion is one of the major susceptible organelles that get damaged during cryopreservation. The study aimed to minimize mitochondrial dysfunction and oxidative stress during sperm cryopreservation using mitochondria-specific antioxidants. For this, semen was collected from five buffalo bulls (3 ejaculates/bull). The ejaculates were diluted in an low-density lipoprotein-based extender and divided into four equal aliquots. Mitochondria-targeted antioxidant (MitoQ) was added at a final concentration of 0 (control), 0.02, 0.2 and 2 μM separately in each aliquotes and cryopreserved. The addition of MitoQ at a concentration of 0.02 μM improved post-thaw sperm motility, plasma membrane integrity and able to sustain sperm motility for a longer time. To investigate MitoQ's effects on mitochondrial function, we measured mitochondrial membrane potential (MMP) using JC-1 dye, superoxide production using Mitosox assay, and lipid peroxidation by TBARS assay. The supplementation of 0.02 μM MitoQ in the extender prevented the significant reduction of MMP and reduced superoxide production resulting in lower lipid peroxidation of sperm plasma membrane after cryopreservation. Further, we found that a higher concentration of MitoQ decreases MMP and increases mitochondrial superoxide production. In conclusion, MitoQ @ 0.02 μM can alleviate oxidative stress by regulating mitochondrial functionality in spermatozoa during cryopreservation.

Semen ejaculates were collected from Murrah buffalo (Bubalus bubalis) bulls and were diluted with low density lipoprotein (LDL) based extender into 20 million sperm/0.25 mL and 2 million sperm/0.25 mL. Dinitrophenol (DNP) was added (@ 0, 1, 10 and 50 µM) to 20 million and 2 million sperm concentration cryopreserved. After thawing, the parameters studied were plasma membrane integrity by HOST, sperm motility and kinetics by CASA, the thermal resistance of sperm by incubation test, mitochondrial superoxide status by MitoSOX through flow cytometry, mitochondrial membrane potential (MMP) evaluation by JC-1 through flow cytometry. There was no significant (P>0.05) change in plasma membrane integrity, sperm motility and kinematics; thermal resistance of sperm, mitochondrial superoxide status and hMMP in comparison to control within the 2 and 20 million sperm doses. Two million sperm doses resulted in low plasma membrane integrity, low thermal resistance of sperm, high mitochondrial superoxide status and decreased high MeMP and no significant (P>0.05) change in sperm motility and kinematics, but reduced total motility, beat cross frequency and no change in progressive motility, straight linear velocity, average path velocity, curvilinear velocity, the amplitude of lateral head displacement, straightness, linearity, and wobble in comparison to 20 million sperm doses. Supplementation of DNP (0, 1, 10 and 50 μM) in extender failed to improve semen quality in both 2 and 20 million sperm doses in buffalo.

This study was designed to examine the effects of seminal insulin-like growth factor-1 (IGF-1) supplementation on structural and functional properties of buffalo sperm post cryopreservation. Semen ejaculates from buffalo bulls (n = 6) were proportioned into four aliquots and diluted with egg yolk-based extender. Prior to equilibration, IGF-1 was added to extender as four treatments: group IGF0 (no supplementation), IGF150 (150 ng/mL), IGF250 (250 ng/mL) and IGF350 (350 ng/mL). The extended semen was transferred into 0.25 mL mini-straws, equilibrated (4 °C at 4 h), and cryopreserved. Total sperm motility was greater (P < 0.05) when there was the IGF150 treatment compared with values for other groups. Furthermore, with the IGF150 treatment there was the least and greatest (P < 0.05) mitochondrial superoxide status and membrane potential, respectively. Similarly, with the IGF150 treatment there was a greater (P < 0.05) sperm membrane integrity with a lesser (P < 0.05) calcium status compared to values for the other groups. In conclusion, seminal IGF-1 supplementation affects the structural and functional properties of buffalo sperm following cryopreservation.

A technology for systemic and repeated administration of osteogenic factors for orthopedic use is an unmet medical need. Lactoferrin (∼80 kDa), present in milk, is known to support bone growth. We discovered a lactoferrin-mimetic peptide, LP2 (an 18-residue fragment from the N-terminus of the N-lobe of human lactoferrin), which self-assembles into a nano-globular assembly with a β-sheet structure in an aqueous environment. LP2 is non-hemolytic and non-cytotoxic against human red blood cells and 3T3 fibroblasts, respectively, and appreciably stable in the human serum. LP2 through the bone morphogenetic protein-dependent mechanism stimulates osteoblast differentiation more potently than the full-length protein as well as the osteoblastic production of osteoprotegerin (an anti-osteoclastogenic factor). Consequently, daily subcutaneous administration of LP2 to rats and rabbits with osteotomy resulted in faster bone healing and stimulated bone formation in rats with a low bone mass more potently than that with teriparatide, the standard-of-care osteogenic peptide for osteoporosis. LP2 has skeletal bioavailability and is safe at the 15× osteogenic dose. Thus, LP2 is a novel peptide that can be administered systemically for the medical management of hard-to-heal fractures.

Background The role of club cells in the pathology of idiopathic pulmonary fibrosis (IPF) is not well understood. Protein disulfide isomerase A3 (PDIA3), an endoplasmic reticulum-based redox chaperone required for the functions of various fibrosis-related proteins; however, the mechanisms of action of PDIA3 in pulmonary fibrosis are not fully elucidated. Objectives To examine the role of club cells and PDIA3 in the pathology of pulmonary fibrosis and the therapeutic potential of inhibition of PDIA3 in lung fibrosis. Methods Role of PDIA3 and aberrant club cells in lung fibrosis was studied by analyses of human transcriptome dataset from Lung Genomics Research Consortium, other public resources, the specific deletion or inhibition of PDIA3 in club cells and blocking SPP1 downstream of PDIA3 in mice. Results PDIA3 and club cell secretory protein (SCGB1A1) signatures are upregulated in IPF compared with control patients. PDIA3 or SCGB1A1 increases also correlate with a decrease in lung function in patients with IPF. The bleomycin (BLM) model of lung fibrosis showed increases in PDIA3 in SCGB1A1 cells in the lung parenchyma. Ablation of Pdia3, specifically in SCGB1A1 cells, decreases parenchymal SCGB1A1 cells along with fibrosis in mice. The administration of a PDI inhibitor LOC14 reversed the BLM-induced parenchymal SCGB1A1 cells and fibrosis in mice. Evaluation of PDIA3 partners revealed that SPP1 is a major interactor in fibrosis. Blocking SPP1 attenuated the development of lung fibrosis in mice. Conclusions Our study reveals a new relationship with distally localised club cells, PDIA3 and SPP1 in lung fibrosis and inhibition of PDIA3 or SPP1 attenuates lung fibrosis.

Mitochondria regulate a myriad of cellular functions. Dysregulation of mitochondrial control within airway epithelial cells has been implicated in the pro-inflammatory response to allergens in asthma patients. Because of their multifaceted nature, mitochondrial structure must be tightly regulated through fission and fusion. Dynamin Related Protein 1 (DRP1) is a key driver of mitochondrial fission. During allergic asthma, airway epithelial mitochondria appear smaller and structurally altered. The role of DRP1-mediated mitochondrial fission, however, has not been fully elucidated in epithelial response to allergens. We used a Human Bronchial Epithelial Cell line (HBECs), primary Mouse Tracheal Epithelial Cells (MTECs), and conditional DRP1 ablation in lung epithelial cells to investigate the impact of mitochondrial fission on the pro-inflammatory response to house dust mite (HDM) in vitro and in vivo. Our data suggest that, following HDM challenge, mitochondrial fission is rapidly upregulated in airway epithelial cells and precedes production of pro-inflammatory cytokines and chemokines. Further, deletion of Drp1 in lung epithelial cells leads to decreased fission and enhanced pro-inflammatory signaling in response to HDM in vitro, as well as enhanced airway hyper-responsiveness (AHR), inflammation, differential mucin transcription, and epithelial cell death in vivo. Mitochondrial fission, therefore, regulates the lung epithelial pro-inflammatory response to HDM.

The present study aimed to compensate dilution effect using additional seminal plasma (SP) in conventional (80 million (M) spermatozoa/ml) dose and low spermatozoa/dose (8M spermatozoa/ml). We also attempted to confirm whether removal of SP before the extension of ejaculates affects post-thaw sperm quality of buffalo semen. For this, semen ejaculates (N = 15) were divided into four groups: control (CON), removal of SP by centrifugation (NSP), resuspension of the centrifuged semen pellet into SP (CEN) and extra supplementation of SP (ESP). All groups were diluted into two different semen doses to 20 and 2M spermatozoa/0.25 ml using tris egg yolk extender and subsequently cryopreserved. We found that neither addition nor removal of SP affected sperm motility, kinematics, longevity, mitochondrial superoxide production and high mitochondrial membrane potential (MMP). Further, the addition or removal of SP was not able to compensate dilution effect in 2M groups resulting in a significantly (p < .05) reduction in sperm motility, kinematics, sperm longevity, membrane integrity, MMP, and an increase production of mitochondrial superoxide. In conclusion, it appears that role of SP in the sperm cryopreservation process is insignificant.

Conjugated bile acids (CBAs), such as tauroursodeoxycholic acid (TUDCA). are known to resolve the inflammatory and unfolded protein response (UPR) in inflammatory diseases, such as asthma. Whether CBAs exert their beneficial effects on allergic airway responses via 1 arm or several arms of the UPR, or alternatively through the signaling pathways for conserved bile acid receptor. remains largely unknown. We used a house dust mite-induced (HDM-induced) murine model of asthma to evaluate and compare the effects of 5 CBAs and 1 unconjugated bile acid in attenuating allergen-induced UPR and airway responses. Expression of UPR-associated transcripts was assessed in airway brushings from human patients with asthma and healthy subjects. Here we show that CBAs, such as alanyl beta-muricholic acid (A beta W) and TUDCA, significantly decreased inflammatory, immune, and cytokine responses; mucus metaplasia; and airway hyperresponsiveness, as compared with other CBAs in a model of allergic airway disease. CBAs predominantly bind to activating transcription factor 6 alpha (ATF6 alpha) compared with the other canonical transducers of the UPR, subsequently decreasing allergen-induced UPR activation and resolving allergic airway disease, without significant activation of the bile acid receptors. TUDCA and A beta M also attenuated other MOM-induced ER stress markers in the lungs of allergic mice. Quantitative mRNA analysis of airway epithelial brushings from human subjects demonstrated that several ATF6 alpha-related transcripts were significantly upregulated in patients with asthma compared with healthy subjects. Collectively, these results demonstrate that CBA-based therapy potently inhibits the allergen-induced UPR and allergic airway disease in mice via preferential binding of the canonical transducer of the UPR, ATF6 alpha. These results potentially suggest a novel avenue to treat allergic asthma using select CBAs.