Anti-Neuroinflammatory Meroterpenoids from a Chinese Collection of the Brown Alga Sargassum siliquastrum.

Nine new chromane-type meroterpenoids, including the rare nor-meroterpenoid sargasilol A (1) and the eight meroditerpenoids sargasilols B-I (2-9), were isolated from a China Sea collection of the brown alga Sargassum siliquastrum, together with six known analogues (10-15). The structures of the new chromanes were identified by extensive spectroscopic analysis and by comparison with previously reported data. Compounds 1-3 and 6-15 exhibited inhibition against LPS-induced NO production in BV-2 microglial cells, and 1, with a shorter carbon chain, was the most active one. Compound 1 was established as an anti-neuroinflammatory agent through targeting the IKK/IκB/NF-κB signaling pathway. As such, the chromanes from brown algae could provide promising anti-neuroinflammatory lead compounds for further structural modification.

Antioxidant and Neuroprotective Xenicane Diterpenes from the Brown Alga Dictyota coriacea.

Five new xenicane diterpenes, including three rare nitrogen-containing derivatives, dictyolactams A (1) and B (2) and 9-demethoxy-9-ethoxyjoalin (3), a rare diterpene with a cyclobutanone moiety, named 4-hydroxyisoacetylcoriacenone (4), and 19-O-acetyldictyodiol (5), were isolated from an East China Sea collection of the brown alga Dictyota coriacea, along with 15 known analogues (6-20). The structures of the new diterpenes were elucidated by spectroscopic analyses and theoretical ECD calculations. All compounds had cytoprotective effects against oxidative stress in neuron-like PC12 cells. The antioxidant mechanism of 18-acetoxy-6,7-epoxy-4-hydroxydictyo-19-al (6) was related to the activation of Nrf2/ARE signaling pathway; it also showed significant neuroprotective effects against cerebral ischemia-reperfusion injury (CIRI) in vivo. This study provided xenicane diterpene as a promising lead scaffold for the development of potent neuroprotective agents against CIRI.

Morphology, molecular phylogeny and systematics of the diatom genus Fallacia (Sellaphoraceae), with descriptions of three new species1.

Fallacia is distinguished morpho-anatomically from Navicula sensu lato based on the possession of an H-shaped chloroplast, lateral sterna and a finely porous conopeum, but whether this genus is monophyletic is still in question. Three new Fallacia species are described based on morphology and SSU rRNA and rbcL gene sequences: Fallacia tateyamensis sp. nov., Fallacia bosoensis sp. nov. and Fallacia laevis sp. nov. We performed the first comprehensive molecular and morphological phylogenetic analyses of 31 Fallacia species based on 11 new sequences from six species and 23 morphological characters. We also documented the detailed morphogenesis of Fallacia for the first time. Fallacia is not monophyletic. Both morphological and DNA sequence data supported the separation of Rossia from Fallacia, while the phylogenetic position of Pseudofallacia is uncertain. We recognized four morphogroups in Fallacia by morphological and molecular phylogenetic analyses. Ancestral character reconstruction indicated that diatoms in Sellaphoraceae evolved from the possession of two lateral narrow parallel depressions covered by narrow nonporous conopea, to lyre-shaped canals covered by wide porous conopea. Lanceolate canals and the presence of areolae in canals evolved multiple times independently.

Transmembrane protein 88 inhibits transforming growth factor-ß1-induced-extracellular matrix accumulation and epithelial-mesenchymal transition program in human pleural mesothelial cells through modulating TGF-ß1/Smad pathway.

Pleural fibrosis is an irreversible pathological process occurred in the development of several lung diseases. TMEM88 is a member of transmembrane (TMEM) family and has been found to be involved in the regulation of fibrogenesis. However, the role of TMEM88 in pleural fibrosis remains unknown. In this study, we aimed to explore the role of TMEM88 in pleural fibrosis in vitro using transforming growth factor-ß1 (TGF-ß1)-induced human pleural mesothelial cell line MeT-5A cells. Our results showed that the expression levels of TMEM88 were downregulated in pleural fibrosis tissues and TGF-ß1-treated Met-5A cells. Overexpression of TMEM88 inhibited the proliferation of Met-5A cells under TGF-ß1 stimulation. In addition, TMEM88 overexpression prevented TGF-ß1-induced extracellular matrix (ECM) accumulation and epithelial-mesenchymal transition (EMT) in Met-5A cells with decreased expression levels of Col I and fibronectin, increased levels of cytokeratin-8 and E-cadherin, as well as decreased levels of vimentin and α-SMA. Furthermore, overexpression of TMEM88 inhibited the expression of TGF-ß receptor I (TßRI) and TßRII and suppressed the phosphorylation of Smad2 and Smad3 in Met-5A cells. In conclusion, these results indicated that TMEM88 exhibited an anti-fibrotic activity in pleural fibrosis via inhibiting the activation of TGF-ß1/Smad signaling pathway.

Hydroazulene Diterpenes from a Dictyota Brown Alga and Their Antioxidant and Neuroprotective Effects Against Cerebral Ischemia-Reperfusion Injury.

Five new diterpenes, including four new hydroazulenes, (8R,11R)-8,11-diacetoxypachydictyol A (1), (8R*,11R*)-6-O-acetyl-8-acetoxy-11-hydroxypachydictyol A (2), (8R*,11S*)-8-acetoxy-11-hydroxypachydictyol A (3), and (8R*,11S*)-6-O-acetyl-8,11-dihydroxypachydictyol A (4), and a secohydroazulene derivative, named 7Z-7,8-seco-7,11-didehydro-8- acetoxypachydictyol A (5), were isolated from a South China Sea collection of a Dictyota sp. nov. brown alga, together with five known analogues (6-10). Structure elucidation was achieved by extensive spectroscopic analysis and comparison with reported data. All compounds showed potent antioxidant effects against H2O2-induced oxidative damage in neuron-like PC12 cells at a low concentration of 2 µM. The antioxidant property of dictyol C (9) was associated with activation of the Nrf2/ARE signaling pathway; it also showed neuroprotective effects against cerebral ischemia-reperfusion injury (CIRI) in a rat model of transient middle cerebral artery occlusion. As such, hydroazulene diterpenes could serve as lead structures for the development of novel neuroprotective agents against CIRI.

Pentraxin 3 (PTX-3) Levels in Bronchoalveolar Lavage Fluid as a Lung Cancer Biomarker.

In this study, we investigated the utility of pentraxin 3 (PTX-3) in bronchoalveolar lavage fluid (BALF) as lung cancer (LCa) diagnostic. A total of 89 LCa patients and 84 non-LCa patients who received bronchoscopy in the First Affiliated Hospital of Xi'an Jiaotong University from December 2014 to February 2015 were enrolled. LCa was subdivided according to pathological type (scale, gland, and small cell lung cancer). BALF samples were obtained during bronchoscopy and PTX-3 levels assayed by ELISA. t-tests, Mann-Whitney, and Kruskal-Wallis tests were performed for the comparison of PTX-3 levels between the different groups. Correlation analysis and receiver operating characteristic (ROC) analysis were used to analyze clinical data. The levels of PTX-3 increased in the LCa groups. PTX-3 levels were higher in the small cell lung cancer (SCLC) compared to non-small-cell lung cancer (NSCLC) groups. In LCa patients, obstructive pneumonia could upregulate the expression of PTX-3 in BALF. The area under the ROC curve of PTX-3 in BALF during LCa diagnosis, SCLC, and LCa with obstructive pneumonia was 0.949 (p ≤ 0.001), 0.672 (p < 0.05), and 0.838 (p < 0.01), respectively. In conclusion, PTX-3 in BALF has a potential value as an LCa biomarker, particularly in cases of SCLC and LCa with obstructive pneumonia.

Analysis of the current status of pelvic floor dysfunction in urban women in Xi'an City.

BACKGROUND: Female pelvic floor dysfunction (PFD), a common disease affecting women, has attracted a significant amount of attention in the field of obstetrics and gynecology in recent years. Pelvic floor disorders can induce urinary incontinence, vaginal prolapse and other dysfunction, which seriously affect the quality of life of patients. This study aimed to analyze the current status of PFD in urban women in Xi'an City. METHODS: A total of 1300 women in the urban area of Xi'an City were selected based on a multi-stage sampling method. A face-to-face questionnaire survey and gynecological examination were carried out, and the prevalence rates of stress urinary incontinence (SUI) and pelvic organ prolapse (POP) and PFD were calculated, Multivariate logistic regression analysis was performed to analyze the risk factors of PFD in urban women in Xi'an City. RESULTS: The effective questionnaire recovery rate was 76.69% (997/1,300). The number of patients with SUI, POP, and SUI combined POP were 124 (55.11%), 64 (28.44%) and 37 (16.44%), respectively, and the prevalence of PFD was 22.57% (225/997). Multivariate logistic regression analysis showed that the risk of PFD in women with vaginal delivery, delivery times ≥2, menopause or prolonged labor was higher than that in women with cesarean section, delivery times of 1, no menopause, or no prolonged labor (P<0.05). CONCLUSIONS: The prevalence rate of PFD in urban women in Xi'an City cannot be ignored, especially women who have experienced vaginal delivery, delivered ≥2 children, menopause, or prolonged labor. It may be necessary to prioritize these women so as to actively prevent and control PFD.

Characterization by Empirical and Computational Methods of Dictyospiromide, an Intriguing Antioxidant Alkaloid from the Marine Alga Dictyota coriacea.

The challenging structural motif of dictyospiromide (1), a spirosuccinimide alkaloid with antioxidant properties that are associated with activation of the Nrf2/ARE signaling pathway, was assigned using contemporary NMR experiments complemented with anisotropic NMR, chiroptical, and computational methodologies. Anisotropic NMR parameters provided critical orthogonal verification of the configuration of the difficult to assign spiro carbon and the other stereogenic centers in 1.

Salidroside inhibits platelet-derived growth factor-induced proliferation and migration of airway smooth muscle cells.

Abnormal proliferation and migration of airway smooth muscle cells (ASMCs) have been found to be important for the airway remodeling during the pathogenesis of asthma. Salidroside a bioactive glucoside that exerts antitumor activity via inhibiting the cell proliferation and migration of cancer cells. The aim of the current study was to evaluate the effects of salidroside on the proliferation and migration of ASMCs. Our results showed that salidroside inhibited the proliferation and migration of ASMCs in response to platelet-derived growth factor (PDGF) stimulation. Salidroside markedly attenuated the PDGF-induced production of matrix metalloproteinase 2 (MMP-2) and MMP-9 in ASMCs. The levels of contractile phenotype markers including smooth muscle α-actin and calponin were reduced in response to PDGF stimulation, which was attenuated by salidroside pretreatment. Salidroside diminished the increase in the expression levels of type I collagen and fibronectin in PDGF-stimulated ASMCs. Furthermore, salidroside blocked the PDGF-induced activation of the nuclear factor-κB (NF-κB) pathway in ASMCs. The results suggested that salidroside functionally regulated the proliferation, migration, phenotype plasticity, and extracellular matrix deposition in PDGF-induced ASMCs and the NF-κB pathway might be implicated in the effects of salidroside on ASMCs induced by PDGF.

Phylogeography and genetic connectivity of the marine macro-alga Sargassum ilicifolium (Phaeophyceae, Ochrophyta) in the northwestern Pacific1.

The evolutionary influences of historical and contemporary factors on the population connectivity and phylogeographic structure of a brown seaweed, Sargassum ilicifolium, were elucidated using the nuclear ITS2 and mitochondrial COI markers for the collections newly sampled within its distribution range in the northwestern Pacific (NWP). Significant genetic structure at variable levels was identified between populations (pairwise FST ) and among populations grouped by geographical proximity (ΦCT among regions). The adjacent groups of populations with moderate structure revealed from AMOVA appeared to have high genetic connectivity. However, a lack of genealogical concordance with the geographic distribution was uncovered for S. ilicifolium from the NWP. Such genetic homogeneity is interpreted as a result of the interaction between postglacial recolonization and dynamic oceanic current regimes in the region. Two separated glacial refugia, the South China Sea and the Okinawa Trough, in the marginal seas of east China were recognized based on the presence of endemic haplotypes and high haplotype diversity in the populations at southern China and northeast of Taiwan. Populations persisting in these refugia may have served as the source for recolonization in the NWP with the rise of sea level during the warmer interglacial periods. The role of oceanic currents in maintaining genetic connectivity of S. ilicifolium in the region was further corroborated by the coherence between the direction of oceanic currents and that of gene flow, especially along the eastern coast of Taiwan. This study underlines the interaction between historical postglacial recolonization and contemporary coastal hydrodynamics in contributing to population connectivity and distribution for this tropical seaweed in the NWP.

Characterization of the whole chloroplast genome Caulerpa lentillifera J. Agardh (Bryopsidales, Chlorophyta).

The whole chloroplast genome (cp DNA) sequence of Caulerpa lentillifera J. Agardh has been characterized from Illumina pair-end sequencing. The circular cpDNA was 119,402 bp in length, containing 122 genes, which included 91 protein-coding genes, 28 tRNA genes, and 3 ribosomal RNA genes (four rRNA species). The overall AT content of C. lentillifera cpDNA is 67.4%. The 48 genes phylogenetic analysis suggested that C. lentillifera formed a monophyletic clade with congeneric C. racemosa.

S100A4 amplifies TGF-ß-induced epithelial-mesenchymal transition in a pleural mesothelial cell line.

Pleural fibrosis can dramatically lower the quality of life. Numerous studies have reported that epithelial-mesenchymal transition (EMT) regulated by transforming growth factor-ß (TGF-ß) is involved in fibrosis. However, the molecular mechanism is inadequately understood. Fibroblast-specific protein-1 (S100A4) is a target of TGF-ß signaling. In our previous study, we have reported that S100A4 is highly expressed in pleural fibrosis. Thus, we suggest that S100A4 took part in the TGF-ß-induced EMT in pleural fibrosis. In this study, we determined the expression of S100A4 and EMT-related markers in Met-5A cells (pleural mesothelial cells) treated with TGF-ß or TGF-ß inhibitor by real-time PCR and western blot. In order to explore the role of S100A4, we used siRNA to knock down the expression of S100A4 in cell model. We found that the expression of epithelial cell marker was decreased and the mesenchymal cell marker increased with S100A4 upregulation after treatment with TGF-ß. Moreover, the changes of EMT-related event were restricted when the expression of S100A4 was knocked down. Conversely, S100A4 can partially rescue the EMT-related expression changes induced by TGF-ß inhibitor. These findings suggest that S100A4 expression is induced by the TGF-ß pathway, and silencing S100A4 expression can inhibit the process of TGF-ß-induced EMT.

Historical isolation and contemporary gene flow drive population diversity of the brown alga Sargassum thunbergii along the coast of China.

BACKGROUND: Long-term survival in isolated marginal seas of the China coast during the late Pleistocene ice ages is widely believed to be an important historical factor contributing to population genetic structure in coastal marine species. Whether or not contemporary factors (e.g. long-distance dispersal via coastal currents) continue to shape diversity gradients in marine organisms with high dispersal capability remains poorly understood. Our aim was to explore how historical and contemporary factors influenced the genetic diversity and distribution of the brown alga Sargassum thunbergii, which can drift on surface water, leading to long-distance dispersal. RESULTS: We used 11 microsatellites and the plastid RuBisCo spacer to evaluate the genetic diversity of 22 Sargassum thunbergii populations sampled along the China coast. Population structure and differentiation was inferred based on genotype clustering and pairwise F ST and allele-frequency analyses. Integrated genetic analyses revealed two genetic clusters in S. thunbergii that dominated in the Yellow-Bohai Sea (YBS) and East China Sea (ECS) respectively. Higher levels of genetic diversity and variation were detected among populations in the YBS than in the ECS. Bayesian coalescent theory was used to estimate contemporary and historical gene flow. High levels of contemporary gene flow were detected from the YBS (north) to the ECS (south), whereas low levels of historical gene flow occurred between the two regions. CONCLUSIONS: Our results suggest that the deep genetic divergence in S. thunbergii along the China coast may result from long-term geographic isolation during glacial periods. The dispersal of S. thunbergii driven by coastal currents may facilitate the admixture between southern and northern regimes. Our findings exemplify how both historical and contemporary forces are needed to understand phylogeographical patterns in coastal marine species with long-distance dispersal.

Genetic and morphological analyses of Gracilaria firma and G. changii (Gracilariaceae, Rhodophyta), the commercially important agarophytes in western Pacific.

Many studies classifying Gracilaria species for the exploitation of agarophytes and the development of the agar industry were conducted before the prevalence of molecular tools, resulting in the description of many species based solely on their morphology. Gracilaria firma and G. changii are among the commercially important agarophytes from the western Pacific; both feature branches with basal constrictions that taper toward acute apices. In this study, we contrasted the morpho-anatomical circumscriptions of the two traditionally described species with molecular data from samples that included representatives of G. changii collected from its type locality. Concerted molecular analyses using the rbcL and cox1 gene sequences, coupled with morphological observations of the collections from the western Pacific, revealed no inherent differences to support the treatment of the two entities as distinct taxa. We propose merging G. changii (a later synonym) into G. firma and recognize G. firma based on thallus branches with abrupt basal constrictions that gradually taper toward acute (or sometimes broken) apices, cystocarps consisting of small gonimoblast cells and inconspicuous multinucleate tubular nutritive cells issuing from gonimoblasts extending into the inner pericarp at the cystocarp floor, as well as deep spermatangial conceptacles of the verrucosa-type. The validation of specimens under different names as a single genetic species is useful to allow communication and knowledge transfer among groups from different fields. This study also revealed considerably low number of haplotypes and nucleotide diversity with apparent phylogeographic patterns for G. firma in the region. Populations from the Philippines and Taiwan were divergent from each other as well as from the populations from Malaysia, Thailand, Singapore and Vietnam. Establishment of baseline data on the genetic diversity of this commercially important agarophyte is relevant in the context of cultivation, as limited genetic diversity may jeopardize the potential for its genetic improvement over time.

miR-1254 promotes lung cancer cell proliferation by targeting SFRP1.

Lung cancer is the leading cause of cancer deaths worldwide, many miRNAs play critical role in lung cancer initiation and progression. Here, we demonstrated that miR-1254 was upregulated in lung cancer tissues and cells. miR-1254 overexpression promoted lung cancer cell proliferation determined by MTT assay, colony formation assay, soft agar growth ability assay and BrdU incorporation assay, miR-1254 knockdown suppressed lung cancer cell proliferation. Mechanism analysis revealed that Wnt/ß-catenin pathway antagonist secreted frizzled related protein 1 (SFRP1) was its target, its expression was opposite to SFRP1 level, and directly bound to the 3'UTR of SFRP1. Double knockdown of miR-1254 and SFRP1 promoted lung cancer cell proliferation, suggesting miR-1254 promoted lung cancer cell proliferation by targeting SFRP1.

Polysaccharides and their depolymerized fragments from Costaria costata: Molecular weight and sulfation-dependent anticoagulant and FGF/FGFR signal activating activities.

Crude polysaccharides from Costaria costata were extracted by hot water and further fractionated by anion exchange chromatography into three polysaccharide fractions. Three low molecular weight fragments were then prepared by degradation of the polysaccharides with hydrogen peroxide and ascorbic acid. The structural features of the polysaccharides and their low molecular weight fragments were elucidated for the first time based on the HGPC, FT-IR, NMR, MS, monosaccharide composition, and other chemical analyses. Their anticoagulant and FGF-1, -2, -7, -8, -9, -10/FGFR1c signaling activation activities in BaF3 cells were also examined. Our studies showed that the polysaccharides were sulfated at different positions of galactose and fucose residues. The APTT-, PT- and TT-based anticoagulant assay results indicated that a high molecular weight and a higher degree of sulfation were essential for their anticoagulant activities. In contrast, not only the polysaccharides but also the depolymerized fragments showed significant FGF/FGFR signal activating activities in a FGF-, molecular weight-, and sulfation-dependent manner. The results presented in current study demonstrated the potential use of the polysaccharides and their fragments as anticoagulants and FGF signal regulators.

WITHDRAWN: MicroRNA-505 modulates cancer proliferation and migration in human non-small cell lung cancer through inverse regulation of FZD4.

This article has been withdrawn at the request of the Editor-in-Chief. Following peer-review and acceptance of the above referenced paper for publication in Lung Cancer, the Editor-in-Chief was contacted by the Editor-in-Chief of the journal, Gene Therapy, with information that the manuscript had simultaneously been submitted to both Lung Cancer and Gene Therapy. A referee selected to review the manuscript for Gene Therapy was also contacted by the Editor-in-Chief of the journal, Respiratory Research, with a request to review the same manuscript for that journal. The three journals ascertained that the manuscript had been simultaneously submitted to all three journals. In addition, as part of their investigation of potential simultaneous submission, the Editors of Lung Cancer compared the manuscript submitted to Gene Therapy with that accepted for publication in Lung Cancer, and this has raised concerns related to the data presented in the paper. The paper accepted for publication in Lung Cancer examines A549 and H810 cells. The paper submitted to Gene Therapy examines A549 and H510A cells. However, the data presented in both papers, including the figures, are identical. The Editors of Lung Cancer have asked the authors for an explanation, but the corresponding author has not responded. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Hidden diversity and phylogeographic history provide conservation insights for the edible seaweed Sargassum fusiforme in the Northwest Pacific.

Understanding the evolutionary processes that have created diversity and the genetic potential of species to adapt to environmental change is an important premise for biodiversity conservation. Herein, we used mitochondrial trnW-L and cox3 and plastid rbcL-S data sets to analyze population genetic variation and phylogeographic history of the brown alga Sargassum fusiforme, whose natural resource has been largely exterminated in the Asia-Northwest Pacific in the past decades. Phylogenetic trees and network analysis consistently revealed three major haplotype groups (A, B, and C) in S. fusiforme, with A and B distributed in the Japan-Pacific coast. Group C consisted of three subgroups (C1, C2, and C3) which were distributed in the Sea of Japan, the Yellow-Bohai Sea, and East China Sea, respectively. Isolation-with-migration (IM a) analysis revealed that the three groups diverged approximately during the mid-Pleistocene (c. 756-1,224 ka). Extended Bayesian skyline plots (EBSP) showed that groups A and B underwent relatively long-term stable population size despite a subsequent rapid demographic expansion, while subgroups C2 and C3 underwent a sudden expansion at c. 260 ka. FST and AMOVA detected low population-level genetic variation and high degrees of divergence between groups. The cryptic diversity and phylogeographic patterns found in S. fusiforme not only are essential to understand how environmental shifts and evolutionary processes shaped diversity and distribution of coastal seaweeds but also provide additional insights for conserving and managing seaweed resources and facilitate predictions of their responses to future climate change and habitat loss.

Historical biogeography of the highly diverse brown seaweed Lobophora (Dictyotales, Phaeophyceae).

The tropical to warm-temperate marine brown macroalgal genus Lobophora (Dictyotales, Phaeophyceae) recently drew attention because of its striking regional diversity. In this study we reassess Lobophora global species diversity, and species distributions, and explore how historical factors have shaped current diversity patterns. We applied a series of algorithmic species delineation techniques on a global mitochondrial cox3 dataset of 598 specimens, resulting in an estimation of 98-121 species. This diversity by far exceeds traditional diversity estimates based on morphological data. A multi-locus time-calibrated species phylogeny using a relaxed molecular clock, along with DNA-confirmed species distribution data was used to analyse ancestral area distributions, dispersal-vicariance-founder events, and temporal patterns of diversification under different biogeographical models. The origin of Lobophora was estimated in the Upper Cretaceous (-75 to -60 MY), followed by gradual diversification until present. While most speciation events were inferred within marine realms, founder events also played a non-negligible role in Lobophora diversification. The Central Indo-Pacific showed the highest species diversity as a result of higher speciation events in this region. Most Lobophora species have small ranges limited to marine realms. Lobophora probably originated in the Tethys Sea and dispersed repeatedly in the Atlantic (including the Gulf of Mexico) and Pacific Oceans. The formation of the major historical marine barriers (Terminal Tethyan event, Isthmus of Panama, Benguela upwelling) did not act as important vicariance events. Long-distance dispersal presumably represented an important mode of speciation over evolutionary time-scales. The limited geographical ranges of most Lobophora species, however, vouch for the rarity of such events.

Tunicamycin aggravates endoplasmic reticulum stress and airway inflammation via PERK-ATF4-CHOP signaling in a murine model of neutrophilic asthma.

INTRODUCTION: Endoplasmic reticulum (ER) stress has been considered to be an important regulator of airway inflammation in the pathogenesis of bronchial asthma, but the mechanism of ER stress involved in neutrophilic asthma remain not fully understood. METHODS: Tunicamycin is a mixture of homologous nucleoside antibiotics, which is used to induce ER stress. In the present study, Tunicamycin was administered to mouse bronchial epithelial cells and a neutrophilic asthma model (OVALPS-OVA mice), and ER stress indicators and inflammatory cytokines were measured by Western blotting and Elisa. RESULTS: Tunicamycin not only induced ER stress in mouse bronchial epithelial cells, but also increased expression of inflammation indicators such as IL-6, IL-8, and TNF-α via PERK-ATF4-CHOP signaling. Additionally, the phosphorylation of PERK and the expression levels of ATF4 and CHOP proteins and inflammatory cytokines (IL-6, IL-8 and TNF-α) were elevated in the lung tissue of OVALPS-OVA mice. Administering tunicamycin further increased protein expression levels of ER stress indicators and inflammatory cytokines, and resulted in more severe asthma phenotypes in OVALPS-OVA mice, suggesting that PERK-ATF4-CHOP signaling is associated with airway inflammation in neutrophil-dominant asthma. CONCLUSIONS: These data support the emerging notion that regulation of ER stress could be strongly associated with the development of neutrophilic asthma.