Functional effects of Toll-like receptor (TLR)3, 7, 9, RIG-I and MDA-5 stimulation in nasal epithelial cells

• Published in: PloS one 2014-06, Vol.9 (6), p.e98239-e98239
• Main Authors: Tengroth, Lotta, Millrud, Camilla Rydberg, Kvarnhammar, Anne Månsson, Kumlien Georén, Susanna, Latif, Leith, Cardell, Lars-Olaf
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Allergic rhinitis; Allergies; Analysis; Asthma; Biology and Life Sciences; Biopsy; Biotechnology; Cell Line; Cell lines; Clinical Medicine; CpG islands; Cytokines; Cytometry; DEAD Box Protein 58; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; Enzyme-linked immunosorbent assay; Epithelial cells; Epithelial Cells - metabolism; Epithelium; Epithelium - metabolism; Female; Flow cytometry; Gene expression; Granulocyte-macrophage colony-stimulating factor; Humans; Immune response; Immune system; Immunohistochemistry; Immunology; Infections; Inflammation; Inflammatory diseases; Interferon; Interferon-Induced Helicase, IFIH1; Interleukin 6; Interleukin 8; Intrusion; Klinisk medicin; Laboratories; Lungmedicin och allergi; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicine and Health Sciences; Melanoma; Metastasis; Microorganisms; Mucosa; Nasal Mucosa - metabolism; Nose - cytology; Otolaryngology; Pathogenesis; Pattern recognition; Penicillin; Poly (I:C); Proteins; Receptors; Receptors, Immunologic; Respiratory Medicine and Allergy; Respiratory tract; Respiratory tract diseases; Reverse transcription; Rhinitis; Rhinosinusitis; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stimulation; TLR3 protein; Toll-like receptors; Toll-Like Receptors - genetics; Toll-Like Receptors - metabolism; Viral infections; Viruses; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0098239

The human nasal epithelium is an important physical barrier, and a part of the innate immune defense that protect against pathogens. The epithelial cells recognize microbial components by pattern-recognition receptors (PRRs), and thereby trigger an immune response. Even though TLR3, TLR7, TLR9, RIG-I and MDA-5 are all known to respond to viral stimulation, their potential role in chronic airway inflammation triggered by local cytokine release remains to be established. mRNA and corresponding protein expression of TLR3, TLR7, TLR9, RIG-I and MDA-5 were analyzed in nasal biopsies and various upper airway epithelial cell lines using real-time reverse transcription PCR, immunohistochemistry and flow cytometry. Ligand induced, cytokine release, was evaluated with ELISA. Nasal biopsies were found to express TLR3, TLR7, TLR9, RIG-I and MDA-5, with the most abundant expression in the surface epithelium. These receptors were verified in primary human nasal epithelial cell (HNEC) as well as in the airway epithelial cell lines Detroit-562 and FaDu. Poly(I:C) (TLR3) and R-837 (TLR7) stimulation increased secretion of IL-6 and GM-CSF from the nasal mucosa and the epithelial cell lines. CpG (TLR9) stimulation caused release of IL-8 in the nasal mucosa and in FaDu. Poly(I:C)/LyoVec (RIG-I/MDA-5) stimulation activated the secretion of IFN-β in the nasal mucosa. A corresponding release was also detected from HNEC and Detroit-562. The nasal epithelium has the ability to recognize viral intrusion through TLR and RLR receptors, and the subsequent response might have a role in exacerbation of inflammatory diseases like allergic rhinitis and chronic rhinosinusitis.