Enhanced inhibition of nasal epithelial cell repair by innate stimulation in patients with allergic rhinitis

• Authors: Anna Lewandowska-Polak , Małgorzata Brauncajs , Marzena Jarzębska , Agnieszka Olszewska-Ziąber , Janna Makowska , Marek L. Kowalski

Title variants

PL

Zwiększone hamowanie naprawy komórek nabłonka nosa przez stymulację nieswoistą u pacjentów z alergicznym zapaleniem błony śluzowej nosa

• Languages of publication: EN PL

Abstracts

EN

Introduction. Impaired repair of airway epithelium may lead to persistence of inflammation and remodelling. Regeneration of injured epithelium is a complex phenomenon and the role of toll-like receptors (TLRs) and respiratory virus products in this process have not been established. Aim of the study. In this study we aimed to test if wound repair in nasal epithelial cells is modulated by microbial products and if this process was different in patients with allergic rhinitis and in healthy subjects. Materials and methods. Injured human nasal epithelial cells (hNECs) monolayers were incubated with the toll-like receptors agonists: poly (I:C) and lipopolisacharide (LPS); allergen Der p1, and supernatants from virus-infected epithelial cells. Regeneration of injured epithelium was assessed by measuring changes in the area of epithelial damage. Results. Addition of either poly (I:C) or LPS induced a dose dependant inhibition of wound repair in hNECs monolayers. Supernatants from RV1b-infected cells decreased epithelial cell regeneration after mechanical injury only in allergic patients. At baseline conditions the dynamics of epithelial repair was similar in allergic and non-allergic epithelium. However, inhibitory effects of innate stimuli on epithelial repair was stronger in patients with allergic rhinitis as compared to healthy individuals. Conclusions. This study showed that microbial products may affect regeneration of the nasal epithelium, and allergic patients are more susceptible to suppression of epithelial regeneration.

PL

Wprowadzenie. Upośledzenie regeneracji nabłonka dróg oddechowych może prowadzić do utrzymywania się stanu zapalnego i zapoczątkowywać przebudowę błony śluzowej. Proces regeneracji jest zjawiskiem złożonym i nie w pełni poznanym, a rola stymulacji receptorów toll-podobnych (TLR) w tym procesie nie została określona. Cel pracy. Ocena wpływu produktów drobnoustrojów na regenerację nabłonka górnych dróg oddechowych i porównanie regeneracji u osób chorych na alergiczny nieżyt nosa i osób zdrowych. Materiał i metody. Komórki nabłonka nosa pobrane od osób chorych na alergiczny nieżyt nosa i zdrowych hodowano do zlewności, a następnie uszkadzano mechanicznie. Do uszkodzonych hodowli dodawano agonistów receptorów toll-podobnych: poli (I:C) lub lipopolisacharyd (LPS), supernatant z komórek nabłonkowych zakażonych rinowirusem lub alergen Der p1. Regenerację komórek oceniano poprzez powierzchnię uszkodzenia. Wyniki. Inkubacja uszkodzonych hodowli z poli (I:C) lub lipopolisacharydem powodowała hamowanie naprawy nabłonka. Dodanie nadsączu z hodowli zakażonych rinowirusem również hamowało regenerację u chorych na alergiczny nieżyt nosa. Silniejsze zahamowanie stwierdzono u osób chorych na alergiczny nieżyt nosa niż u osób zdrowych. Wniosek. Produkty drobnoustrojów wywierały efekt modulujący regenerację nabłonka nosa, a osoby atopowe były bardziej podatne na zahamowanie regeneracji nabłonka.

Keywords

EN

LPS; TLRs; poly (I:C); nasal epithelium; wound repair

Discipline

• MEDICINE: MEDICINE

• Publisher: Oficyna Wydawnicza Mediton
• Journal: Alergia Astma Immunologia - przegląd kliniczny
• Year: 2019
• Volume: 24
• Issue: 1
• Pages: 18-23

Contributors

author

Anna Lewandowska-Polak

• Department of Rheumatology, Medical University of Lodz

author

Małgorzata Brauncajs

• Department of Microbiology, Immunology and Laboratory Medicine, Chair of Clinical Immunology and Microbiology, Medical University of Lodz

author

Marzena Jarzębska

• Department of Immunology and Allergy, Medical University of Lodz

author

Agnieszka Olszewska-Ziąber

• Department of Immunology and Allergy, Medical University of Lodz

author

Janna Makowska

• Department of Rheumatology, Medical University of Lodz

author

Marek L. Kowalski

• Department of Immunology and Allergy, Medical University of Lodz

References

• Grainge CL, Davies DE. Epithelial injury and repair in airways diseases. Chest 2013; 144: 1906-12.
• Xiao H, Li DX, Liu M. Knowledge translation: airway epithelial cell migration and respiratory diseases. CMLS 2012; 69: 4149-62.
• Laitinen LA, Heino M, Laitinen A, et al. Damage of the airway epithelium and bronchial reactivity in patients with asthma. Am Rev Respir Dis 1985; 131: 599-606.
• Kelly MM, Leigh R, Bonniaud P, et al. Epithelial expression of profibrotic mediators in a model of allergen-induced airway remodeling. Am J Respir Cell Mol Biol 2005; 32: 99-107.
• Begnaud S, Chen T, Delacour D, et al. Mechanics of epithelial tissues during gap closure. Curr Opin Cell Biol 2016; 42: 52-62.
• Loxham M, Davies DE, Blume C. Epithelial function and dysfunction in asthma. Clin Exp Allergy 2014; 44: 1299-313.
• Georas SN, Rezaee F. Epithelial barrier function: at the front line of asthma immunology and allergic airway inflammation. J Allergy Clin Immunol 2014; 134: 509-20.
• Holgate ST, Wenzel S, Postma DS, et al. Asthma. Nat Rev Dis Primers 2015; 10: 15025.
• Holgate ST. The sentinel role of the airway epithelium in asthma pathogenesis. Immunol Rev 2011; 242: 205-19.
• Fahy JV. Type 2 inflammation in asthma--present in most, absent in many. Nature Rev Immunol 2015; 15: 57-65.
• Samitas K, Carter A, Kariyawasam HH, Xanthou G. Upper and lower airway remodelling mechanisms in asthma, allergic rhinitis and chronic rhinosinusitis: The one airway concept revisited. Allergy 2018; 73: 993-1002.
• Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F et al. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004; 118: 229-41.
• Rakoff-Nahoum S, Medzhitov R. Role of toll-like receptors in tissue repair and tumorigenesis. Biochemistry 2008; 73: 555-61.
• Pull SL, Doherty JM, Mills JC, et al. Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury. Proc Natl Acad Sci U.S.A. 2005; 102: 99-104.
• Brown SL, Riehl TE, Walker MR, et al. Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. J Clin Invest 2007; 117: 258-69.
• Lewandowska-Polak A, Brauncajs M, Jarzębska M, et al. Toll-Like Receptor Agonists Modulate Wound Regeneration in Airway Epithelial Cells. Int J Mol Sci 2018; 19(8): 2456.
• Lewandowska-Polak A, Jarzębska M, Brauncajs M, et al. Wound repair and regeneration of upper and lower airway epithelium - validation of experimental methodology. Alergia Astma Immunologia 2016; (21): 162-8.
• Głobinska A, Pawelczyk M, Piechota-Polanczyk A, et al. Impaired virus replication and decreased innate immune responses to viral infections in nasal epithelial cells from patients with allergic rhinitis. Clin Exp Immunol 2017; 187: 100-12.
• Valera FCP, Ruffin M, Adam D, et al. Staphylococcus aureus impairs sinonasal epithelial repair: Effects in patients with chronic rhinosinusitis with nasal polyps and control subjects. J Allergy Clin Immunol 2019; 143: 591-603.e3.
• Nonaka M, Pawankar R, Fukumoto A, Yagi T. Heterogeneous response of nasal and lung fibroblasts to transforming growth factor-beta 1. Clin Exp Allergy 2008; 38: 812-21.
• Xagorari A, Chlichlia K. Toll-like receptors and viruses: induction of innate antiviral immune responses. Open Microbiol J 2008; 2: 4959.
• O'Neill LA, Golenbock D, Bowie AG. The history of Toll-like receptors - redefining innate immunity. Nat Rev Immunol 2013; 13: 453-60.
• Moskwa S, Piotrowski W, Marczak J, et al. Innate Immune Response to Viral Infections in Primary Bronchial Epithelial Cells is Modified by the Atopic Status of Asthmatic Patients. Allergy Asthma Immunol Res 2018; 10: 144-54.
• Whitsett JA, Alenghat T. Respiratory epithelial cells orchestrate pulmonary innate immunity. Nature Immunol 2015; 16: 27-35.
• Ellson CD, Dunmore R, Hogaboam CM, et al. Danger-associated molecular patterns and danger signals in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 2014; 51: 163-8.
• Kang JH, Hwang SM, Chung IY. S100A8, S100A9 and S100A12 activate airway epithelial cells to produce MUC5AC via extracellular signal-regulated kinase and nuclear factor-kappaB pathways. Immunology 2015; 144: 79-90.
• Pouwels SD, Heijink IH, ten Hacken NH, et al. DAMPs activating innate and adaptive immune responses in COPD. Mucosal Immunol 2014; 7: 215-26.
• Olivera DS, Boggs SE, Beenhouwer C, et al. Cellular mechanisms of mainstream cigarette smoke-induced lung epithelial tight junction permeability changes in vitro. Inhal Toxicol 2007; 19: 13-22.
• Petecchia L, Sabatini F, Varesio L, et al. Bronchial airway epithelial cell damage following exposure to cigarette smoke includes disassembly of tight junction components mediated by the extracellular signal-regulated kinase 1/2 pathway. Chest 2009; 135: 1502-12.
• Wan H, Winton HL, Soeller C, et al. The transmembrane protein occludin of epithelial tight junctions is a functional target for serine peptidases from faecal pellets of Dermatophagoides pteronyssinus. Clin Exp Allergy 2001; 31: 279-94.
• Sajjan U, Wang Q, Zhao Y, et al. Rhinovirus disrupts the barrier function of polarized airway epithelial cells. Am Journal of Resp and Critical Care Med 2008; 178: 1271-81.
• Looi K, Troy NM, Garratt LW, et al. Effect of human rhinovirus infection on airway epithelium tight junction protein disassembly and transepithelial permeability. Exp Lung Res 2016; 11: 1-16.
• Bossios A, Psarras S, Gourgiotis D, et al. Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells. Respir Res 2005; 6: 114.
• Faris AN, Ganesan S, Chattoraj A, et al. Rhinovirus Delays Cell Repolarization in a Model of Injured/Regenerating Human Airway Epithelium. Am J Respir Cell Mol Biol 2016; 55: 487-99.
• Hammad H, Chieppa M, Perros F, et al. House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med 2009; 15: 410-6.
• Moller-Larsen S, Nyegaard M, Haagerup A, et al. Association analysis identifies TLR7 and TLR8 as novel risk genes in asthma and related disorders. Thorax 2008; 63: 1064-9.
• Nilsson D, Andiappan AK, Hallden C, et al. Toll-like receptor gene polymorphisms are associated with allergic rhinitis: a case control study. BMC Med Genet 2012; 13: 66.
• Greiff L, Cervin A, Ahlstrom-Emanuelsson C, et al. Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis. Respir Res 2012; 13: 53.
• Wan H, Winton HL, Soeller C, et al. Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions. J Clin Invest 1999; 104: 123-33.
• Winton HL, Wan H, Cannell MB, et al. Class specific inhibition of house dust mite proteinases which cleave cell adhesion, induce cell death and which increase the permeability of lung epithelium. Br
• J Pharmacol 1998; 124: 1048-59.

• Document Type: article