• 제목/요약/키워드: Airway epithelial cells

검색결과 171건 처리시간 0.03초

SARS-CoV-2 Infection of Airway Epithelial Cells

  • Gwanghui Ryu;Hyun-Woo Shin
    • IMMUNE NETWORK
    • /
    • 제21권1호
    • /
    • pp.3.1-3.16
    • /
    • 2021
  • Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide since its outbreak in December 2019, and World Health Organization declared it as a pandemic on March 11, 2020. SARS-CoV-2 is highly contagious and is transmitted through airway epithelial cells as the first gateway. SARS-CoV-2 is detected by nasopharyngeal or oropharyngeal swab samples, and the viral load is significantly high in the upper respiratory tract. The host cellular receptors in airway epithelial cells, including angiotensin-converting enzyme 2 and transmembrane serine protease 2, have been identified by single-cell RNA sequencing or immunostaining. The expression levels of these molecules vary by type, function, and location of airway epithelial cells, such as ciliated cells, secretory cells, olfactory epithelial cells, and alveolar epithelial cells, as well as differ from host to host depending on age, sex, or comorbid diseases. Infected airway epithelial cells by SARS-CoV-2 in ex vivo experiments produce chemokines and cytokines to recruit inflammatory cells to target organs. Same as other viral infections, IFN signaling is a critical pathway for host defense. Various studies are underway to confirm the pathophysiological mechanisms of SARS-CoV-2 infection. Herein, we review cellular entry, host-viral interactions, immune responses to SARS-CoV-2 in airway epithelial cells. We also discuss therapeutic options related to epithelial immune reactions to SARS-CoV-2.

The Role of Proprotein Convertases in Upper Airway Remodeling

  • Lee, Sang-Nam;Yoon, Joo-Heon
    • Molecules and Cells
    • /
    • 제45권6호
    • /
    • pp.353-361
    • /
    • 2022
  • Chronic rhinosinusitis (CRS) is a multifactorial, heterogeneous disease characterized by persistent inflammation of the sinonasal mucosa and tissue remodeling, which can include basal/progenitor cell hyperplasia, goblet cell hyperplasia, squamous cell metaplasia, loss or dysfunction of ciliated cells, and increased matrix deposition. Repeated injuries can stimulate airway epithelial cells to produce inflammatory mediators that activate epithelial cells, immune cells, or the epithelial-mesenchymal trophic unit. This persistent inflammation can consequently induce aberrant tissue remodeling. However, the molecular mechanisms driving disease within the different molecular CRS subtypes remain inadequately characterized. Numerous secreted and cell surface proteins relevant to airway inflammation and remodeling are initially synthesized as inactive precursor proteins, including growth/differentiation factors and their associated receptors, enzymes, adhesion molecules, neuropeptides, and peptide hormones. Therefore, these precursor proteins require post-translational cleavage by proprotein convertases (PCs) to become fully functional. In this review, we summarize the roles of PCs in CRS-associated tissue remodeling and discuss the therapeutic potential of targeting PCs for CRS treatment.

Primary Cilium by Polyinosinic:Polycytidylic Acid Regulates the Regenerative Migration of Beas-2B Bronchial Epithelial Cells

  • Gweon, Bomi;Jang, Tae-Kyu;Thuy, Pham Xuan;Moon, Eun-Yi
    • Biomolecules & Therapeutics
    • /
    • 제30권2호
    • /
    • pp.170-178
    • /
    • 2022
  • The airway epithelium is equipped with the ability to resist respiratory disease development and airway damage, including the migration of airway epithelial cells and the activation of TLR3, which recognizes double-stranded (ds) RNA. Primary cilia on airway epithelial cells are involved in the cell cycle and cell differentiation and repair. In this study, we used Beas-2B human bronchial epithelial cells to investigate the effects of the TLR3 agonist polyinosinic:polycytidylic acid [Poly(I:C)] on airway cell migration and primary cilia (PC) formation. PC formation increased in cells incubated under serum deprivation. Migration was faster in Beas-2B cells pretreated with Poly(I:C) than in control cells, as judged by a wound healing assay, single-cell path tracking, and a Transwell migration assay. No changes in cell migration were observed when the cells were incubated in conditioned medium from Poly(I:C)-treated cells. PC formation was enhanced by Poly(I:C) treatment, but was reduced when the cells were exposed to the ciliogenesis inhibitor ciliobrevin A (CilioA). The inhibition of Beas-2B cell migration by CilioA was also assessed and a slight decrease in ciliogenesis was detected in SARS-CoV-2 spike protein (SP)-treated Beas-2B cells overexpressing ACE2 compared to control cells. Cell migration was decreased by SP but restored by Poly(I:C) treatment. Taken together, our results demonstrate that impaired migration by SP-treated cells can be attenuated by Poly(I:C) treatment, thus increasing airway cell migration through the regulation of ciliogenesis.

히스티딘 중합체가 일차배양 기도 상피세포에서의 뮤신 유리에 미치는 영향 (Effects of Histidine Polymers on Mucin Release from Primary Cultured Airway Epithelial Cells)

  • 전병규;윤인대;이재우;이충재
    • 약학회지
    • /
    • 제54권5호
    • /
    • pp.334-340
    • /
    • 2010
  • We investigated whether poly-L-histidine (PLH) significantly affect mucin release from cultured airway epithelial cells. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled with $^$^3H$$glucosamine for 24 hr and chased for 30 min in the presence of PLH to assess the effect on $^3H$-mucin release. PLH 9,850 and PLH 6,700 specifically inhibit mucin release from airway goblet cells without significant cytotoxicity. This finding suggests that poly-L-histidine might function as an airway mucoregulative agent.

기관지 천식에서의 기도 개형 (Airway Remodelling in Asthma)

  • 임대현
    • Clinical and Experimental Pediatrics
    • /
    • 제48권10호
    • /
    • pp.1038-1049
    • /
    • 2005
  • Asthma is characterized by a chronic inflammatory disorder of the airways that leads to tissue injury and subsequent structural changes collectively called airway remodelling. Characteristic changes of airway remodelling in asthma include goblet cell hyperplasia, deposition of collagens in the basement membrane, increased number and size of microvessels, hypertrophy and hyperplasia of airway smooth muscle, and hypertrophy of submucosal glands. Apart from inflammatory cells, such as eosinophils, activated T cells, mast cells and macrophages, structural tissue cells such as epithelial cells, fibroblasts and smooth muscle cells can also play an important effector role through the release of a variety of mediators, cytokines, chemokines, and growth factors. Through a variety of inflammatory mediators, epithelial and mesenchymal cells cause persistence of the inflammatory infiltrate and induce airway structural remodelling. The end result of chronic airway inflammation and remodelling is an increased thickness of the airway wall, leading to a increased the bronchial hyperresponsiveness and fixed declined lung function.

Compressive stress induces collective migration through cytoskeletal remodelling in nasal polyp epithelium

  • Ji Myung Chung;Seong Gyu Lee;Jae-Sung Nam;Jong-Gyun Ha;Ji Hye Chung;Hyung-Ju Cho;Chang-Hoon Kim;Sang-Nam Lee;Hyungsuk Lee;Joo-Heon Yoon
    • Journal of Rhinology
    • /
    • 제59권1호
    • /
    • pp.49-58
    • /
    • 2021
  • Background: Nasal polyps in the nasal cavity and mucous discharge inside the maxillary sinus exhibit compressive stress on the nasal mucosal epithelium. However, there have been only a few studies on how compressive stress impacts the human nasal mucosal epithelium. Methodology: We investigated the effect of compressive stress on collective migration, junctional proteins, transepithelial electrical resistance, epithelial permeability, and gene expression in well-differentiated normal human nasal epithelial (NHNE) cells and human nasal polyp epithelial (HNPE) cells. Results: NHNE cells barely showed collective migration at compressive stress up to 150 mmH20. However, HNPE cells showed much greater degree of collective migration at a lower compressive stress of 100 mmH20. The cell migration of HNPE cells subjected to 100 mmH2O compression was significantly decreased at day 3 and was recovered to the status prior to the compressive stress by day 7, indicating that HNPE cells are relatively more sensitive to mechanical pressure than NHNE cells. Compressive stress also increased transepithelial electrical resistance and decreased epithelial permeability, indicating that the compressive stress disturbed the structural organization rather than physical interactions between cells. In addition, we found that compressive stress induced gene expressions relevant to airway inflammation and tissue remodelling in HNPE cells. Conclusion: Taken together, these findings demonstrate that compressive stress on nasal polyp epithelium is capable of inducing collective migration and induce increased expression of genes related to airway inflammation, innate immunity, and polyp remodelling, even in the absence of inflammatory mediators.

필용방감길탕이 기도 뮤신의 분비, 생성, 유전자 발현 및 점액 과다 분비에 미치는 영향 (Effect of Piryongbanggamgil-tang on Airway Mucin Secretion, Production, Gene Expression and Hypersecretion of Mucus)

  • 김윤영;민상연;김장현
    • 대한한방소아과학회지
    • /
    • 제28권2호
    • /
    • pp.56-71
    • /
    • 2014
  • Objectives In this study, the author tried to investigate whether piryongbang-gamgil-tang (PGGT) significantly affect in vitro airway mucin secretion, PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production / gene expression from human airway epithelial cells and increase in airway epithelial mucosubstances and hyperplasia of tracheal goblet cells of rats. Materials and Methods For in vitro experiment, confluent RTSE cells were chased for 30 min in the presence of PGGT to assess the effect of PGGT on mucin secretion by enzyme-linked immunosorbent assay (ELISA). Also, effect of PGGT on PMA- or EGFor TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of PGGT and treated with PMA (10 ng/ml) or EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24 hrs, to assess both effect of PGGT on PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production by ELISA and gene expression by reverse transcription-polymerase chain reaction (RT-PCR). For in vivo experiment, the author induced hypersecretion of airway mucus and goblet cell hyperplasia by exposure of rats to $SO_2$ during 3 weeks. Effect of orally-administered PGGT during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats and hyperplasia of goblet cells were assesed by using histopathological analysis after staining the epithelial tissue with alcian blue. Possible cytotoxicities of PGGT in vitro were assessed by examining LDH release from RTSE cells and the rate of survival and proliferation of NCI-H292 cells. In vivo liver and kidney toxicities of PGGT were evaluated by measuring serum GOT/GPT activities and serum BUN/creatinine concentrations of rats after administering PGGT orally. Results (1) PGGT did not affect in vitro mucin secretion from cultured RTSE cells. (2) PGGT significantly inhibited PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions and the expression levels of MUC5AC mRNA from NCI-H292 cells. (3) PGGT decreased the amount of intraepithelial mucosubstances and showed the tendency of expectorating airway mucus already produced. (4) PGGT increased LDH release from RTSE cells. However, PGGT did not show in vivo liver and kidney toxicities and cytotoxicity to NCI-H292 cells. Conclusion The result from this study suggests that PGGT can regulate the production and gene expression of airway mucin observed in diverse respiratory diseases accompanied by mucus hypersecretion and do not show in vivo toxicity to liver and kidney functions after oral administration. Effect of PGGT with their components should be further studied using animal experimental models that reflect the diverse pathophysiology of respiratory diseases through future investigations.

Eupatilin downregulates phorbol 12-myristate 13-acetate-induced MUC5AC expression via inhibition of p38/ERK/JNK MAPKs signal pathway in human airway epithelial cells

  • Cheon, Yoon-Hee;Kim, Min Seob;Kim, Ju-Young;Kim, Dong Hyun;Han, Seung Yoon;Lee, Jae-Hoon
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제24권2호
    • /
    • pp.157-163
    • /
    • 2020
  • Chronic inflammatory airway diseases, such as chronic rhinosinusitis, chronic obstructive pulmonary disease, and asthma, are associated with excessive mucus production. Hence, the regulation of mucus production is important for the treatment of upper and lower airway diseases. Eupatilin is a pharmacologically active ingredient obtained from Artemisia asiatica Nakai (Asteraceae) and exerts potent anti-inflammatory, anti-allergic, and anti-tumor activities. In the present study, we investigated the effect of eupatilin on phorbol 12-myristate 13-acetate (PMA)-induced MUC5AC and MUC5B expression in human airway epithelial cells. We found that eupatilin treatment significantly inhibited PMA-induced mucus secretion in PAS staining. In addition, qRT-PCR results showed that eupatilin dose-dependently decreased the mRNA expression of MUC5AC in human airway epithelial cells. Western blot and immunofluorescence assay also showed that PMA-induced protein expression of MUC5AC was inhibited by eupatilin treatment. Finally, we investigated MAPKs activity after stimulation with PMA using western blot analysis in human airway epithelial cells. The results showed that eupatilin downregulated the levels of phosphorylated p38, ERK, and JNK. In summary, the anti-inflammatory activities of eupatilin, characterized as the suppression of MUC5AC expression and secretion in human airway epithelial cells, were found to be associated with the inhibition of p38/ERK/JNK MAPKs signaling pathway of MUC5AC secretion.

금수육군전(金水六君煎)이 이산화황으로 유발된 흰쥐의 호흡기 점액 및 뮤신생성에 미치는 영향 (Effect of Geumsuyukgunjeon on Airway Mucus Secretion and Mucin Production)

  • 김은진;민상연;김장현
    • 대한한방소아과학회지
    • /
    • 제29권2호
    • /
    • pp.26-36
    • /
    • 2015
  • Objectives In this study, effect of Geumsuyukgunjeon (GYJ) on the increase in airway epithelial mucosubstances of rats with acute bronchitis and EGF-induced MUC5AC mucin production from human airway epithelial cells were investigated. Materials and Methods Hypersecretion of airway mucus was induced by exposure of rats to SO2 during 3 weeks. Effect of orally-administered GYJ during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats was assesed using histopathological analysis after staining the epithelial tissue with PAS-alcian blue. Possible cytotoxicity of GYJ was assessed by examining the potential damage of kidney and liver functions by measuring serum GOT/GPT activities and serum BUN and creatinine concentrations of rats and the body weight gain during experiment, after administering GYJ orally. Effect of GYJ on EGF-induced MUC5AC mucin production from human airway epithelial cells (A549) was investigated. Confluent A549 cells were pretreated for 30 min in the presence of GYJ and treated with EGF (25 ng/ml) for 24 hrs, to assess the effect of GYJ on EGF-induced MUC5AC mucin production using enzyme-linked immunosorbent assay (ELISA). Results (1) GYJ decreased the amount of intraepithelial mucosubstances of trachea of rats. (2) GYJ did not show kidney and liver toxicities and did not affect body weight gain of rats during experiment. (3) GYJ significantly inhibited EGF-induced MUC5AC mucin production from A549 cells. Conclusions The result from the present study suggests that GYJ might control both the mucus hypersecretion in vivo and do not show in vivo toxicity to liver and kidney functions after oral administration and the production of pulmonary mucin.

쿠마린과 인도메타신의 억제작용 쿠마린과 인도메타신의 억제작용 (Suppression of Induced Mucin Production from Human Airway Epithelial Cells by Coumarin and Indomethacin)

  • 이재우;김길동;전병규;이충재
    • 약학회지
    • /
    • 제54권5호
    • /
    • pp.416-421
    • /
    • 2010
  • We examined whether indomethacin, noscapine, coumarin, uridine and betaine affect airway mucin production induced by EGF or TNF-${\alpha}$ from NCI-H292 cells. Cells were pretreated with each agent for 30 min and then stimulated with EGF or TNF-${\alpha}$ for 24 h. Of the five compounds, coumarin suppressed airway mucin production induced by EGF or TNF-${\alpha}$. However, indomethacin suppressed airway mucin production induced by EGF. This result suggests that coumarin and indomethacin can regulate the production of mucin induced by EGF, by directly acting on airway epithelial cells.